The Touissit-Bou Beker Mississippi Valley-type (MVT) district of northeastern Morocco includes five major strata-bound Pb-Zn-Ag deposits that produced, over a century of mining, more than 70 Mt of ore at an average grade of 4.0 wt % Pb, 3.5 wt % Zn, ~1 wt % Cu, and 120 g/t Ag. Economic orebodies are hosted by a 25-m-thick sequence of unmetamorphosed, flat-lying, diagenetically and hydrothermally dolomitized carbonate platform rocks of Aalenian-Bajocian (174–168 Ma) age. The sulfide mineralization consists principally of galena and sphalerite, and occurs as open-space fillings and partial to massive replacements of medium- to coarse-grained dolostones. Throughout the district and surrounding prospects, sulfur isotope compositions of sulfide minerals range from –8.6 to 12.9 CDT ( n = 194) and display spatial and temporal variations characterized by an overall progressive decrease of 34 S values: (1) with advancing paragenetic sequence, and upward stratigraphic position; (2) toward distal prospects; and (3) within single grains from core to rim. Similarly, the distribution of 3 He/ 4 He ratios shows an overall lowering from 0.5 R A to 〈0.01 R A with advancing paragenetic stage. Conversely, lead isotope compositions of galena display fairly uniform 206 Pb/ 204 Pb (18.31–18.37), 207 Pb/ 204 Pb (15.61–15.66), and 208 Pb/ 204 Pb (38.45–38.62) ratios, which contrast significantly with the highly heterogeneous isotopic compositions ( 206 Pb/ 204 Pb = 17.76–18.49, 207 Pb/ 204 Pb = 15.61–15.70, 208 Pb/ 204 Pb = 37.76–39.55) shown by potential metal source rocks. The large variations in 34 S values are explained in terms of inorganic and/or bacteriogenic reduction, at different rates, of seawater sulfate in seawater or pore fluids, in reservoirs both open and closed with respect to sulfate. The highly variable 3 He/ 4 He values reflect different degrees of mixing between mantle and crustal He components along the fluid flow path. Estimated contributions of the mantle-derived ( 4 He) component involved in the mineralizing fluids of the paragenetically early Zn-rich ore-stage I, and in the later Pb-rich main ore-stage II, are in the range of ~3 to 8%. With time, the mantle-derived input to the mineralizing fluids decreased, and contemporaneously the involvement of surface waters increased, consistent with the lowering of 34 S with advancing paragenetic stage. This geochemical evolution toward lower isotopic values indicates that the Touissit-Bou Beker hydrothermal system became exclusively dominated by crustally derived fluids, and probably incorporated at shallower levels the influx of progressively larger volumes of cooler, dilute, and oxidized meteoric waters. Whole-rock and galena lead isotope compositions are consistent with a model in which metals were extracted from the local country rocks, particularly the basement Visean rhyodacites and associated siliciclastic rocks, and from the overlying Triassic to Upper Bajocian sediments. The extraction of lead likely occurred during the late Neogene, coincident with the Messinian salinity crisis and anorogenic alkaline magmatism. Conventional MVT genetic models cannot satisfactorily account for Pb-Zn-Ag ore deposition in the Touissit-Bou Beker district. Accordingly, we propose an alternative model involving a genetic link among extensional tectonics, Neogene-Quaternary mafic magmatism, the Messinian salinity crisis, and formation of the Touissit-Bou Beker deposits. We suggest that this mineralization resulted from the regional circulation of warm saline brines, sourced within the Rif corridor, during Messinian-Tortonian time (11.6–5.3 Ma). Messinian paleogeography would have favored the evaporation of seawater and development of a reflux-circulation system, synchronous with the emplacement of Neogene-Quaternary alkaline magmas. The associated elevated heat flow and subsequent increased geothermal gradient initiated buoyancy-driven fluid convection of downward-flowing Messinian seawater, which ultimately promoted the mobilization of older, high-temperature, rock-buffered basement dense brines stored within the Paleozoic basement, and the formation of base-metal–bearing chloride complexes. Mixing of Messinian seawater and basement-derived hydrothermal brines triggered deposition of Pb- and Zn-rich stage I and II mineralization. The resulting mixed brines were mainly centered on the Touissit Shelf and its flanks, and then flowed laterally away from the basement high, giving rise to the lower grade mineralization of the distal prospects. The predominance of a high heat flow regime centered on a positive paleogeographic structure (i.e., basement high) and more importantly the availability of appropriate sulfur nutrients (i.e., "fertile" vs. biogenic sulfur), may have constituted the critical ore controls that governed the size of the ore deposits. Finally, during late Pb-rich cuboctahedral stage III mineralization, interpreted to have been emplaced during a magmatic interlude contemporaneous with the closure of the Rif corridor and its final exhumation, the hydrothermal system became open to the incursion of meteoric waters; subsequent mixing with deep-seated, reduced, H 2 S-rich, saline waters led to precipitation of the sulfides of stage III mineralization.