The present study was conducted to investigate the effects of repeated treatment with selective dopaminergic agents on the level of methionine-enkephalin (Met-Enk) in rat brain cortex (CTX), hypothalamus, (HYPO), hippocampus (HIPP) and midbrain (MID). Male Sprague-Dawley rats were kept under controlled conditions for at least one week. After adaptation period, rats were randomly assigned into nine groups (7-9 rats per group) for intraperitoneal treatment with dopaminergic agents. Group 1 served as control, while, groups 2, 3 and 4 were treated with either SKF-81297, SCH 23390 or their combination, respectively. Groups 5, 6 and 7 received either LY 171555, (-)-sulpiride or their combination, whereas groups 8 and 9 were treated with nomifensine or selegiline, respectively. One hour after the last injection, rats were sacrificed, brains were removed and dissected into different regions, then extracted and their Met-Enk levels determined by radioimmunoassay (RIA). Administration of SKF-81297 or SCH 23390 significantly elevated Met-Enk levels in all brain regions examined, while their combination elevated Met-Enk levels in HYPO and HIPP only. On the other hand, treatment with LY 171555 or (-)-sulpiride, but not their combination, markedly increased Met-ENK levels in all brain regions investigated, whereas, treatment with nomifensine increased Met-Enk levels in all brain regions investigated, whereas, treatment with selegiline significantly elevated Met-Enk in HYPO, HIPP and MID but not in CTX. These findings clearly indicate that dopaminergic agonists and antagonists alter Met-Enk levels in specific rat brain regions.