14C-Morphine was injected iv in control awake rats or in rats subjected to metabolic alkalosis or acidosis. Ten minutes later, radioactivity was determined within each of seven brain regions, after correction was made for intravascular tracer. In each region, parenchymal radioactivity was correlated positively and significantly (P< 0.05) with arterial bloodpH. Brain radioactivity was twofold to threefold greater in alkalotic rats (meanpH = 7.62) than in acidotic rats (meanpH = 7.16). The results are consistent with thepH-partition hypothesis for drug entry into the brain and indicate that morphine uptake can be increased by elevating the fraction of lipid-soluble uncharged morphine base in blood, by means of alkalosis. The observations may account for an exaggerated morphine-induced analgesia in alkalotic patients.