Cerebrovascular permeability of four modified opioid peptides--[D-Ala2]methionine enkephalin amide, beta-[D-Ala62,14C-Homoarg69]lipotropin 61 -69, alpha-[D-Ala2,14C-Homoarg9]endorphin, and beta-[D-Ala2,14C-Homoarg]endorphin--ranged from 1.4 to 3.9 X 10(-6) centimeters per second in brain regions of the conscous rat. These significant permeabilities should allow the peptides to fill the extracellular brain space with a half time of 3 to 11 minutes, as a result of a step increase in plasma concentration of unbound peptide.