Immunocytofluorescent and microautoradiographic methods were applied to measure met-enkephalin-like immunoreactivity (MELI) and ME receptor binding (MERB) levels in cerebral nuclei of serial brain slices from SHR which received clonidine, alpha-methyldopa and hydralazine at equivalent hypotensive doses. All three drugs increased both MELI and MERB levels in the caudal part of the n. tractus solitarii and its functionally related dorsomedullary nuclei and decreased them in the n. accumbens septi, in accordance with the correspondent change in glucose utilization rates in these nuclei as reported previously. Both CNS-active agents (not hydralazine) also increased MELI and MERB levels in the n. intercalatus and substantia grisea centralis, and they decreased them in the n. ventromedialis hypothalami. Differences in both CNS-active agents were minor. Vasodilative hydralazine alone decreased these levels both in the n. reticularis medialis and n. tegmenti ventralis, and it increased them slightly in the area lateralis hypothalami. The present studies indicate that ME neurons of these dorsomedullary and supramedullary nuclei may act as direct as well as homeostatic controls of blood pressure.