The effects of the opioid peptide dynorphin A (DynA) on phagocytosis in peritoneal macrophages was examined by flow cytometry (FCM). DynA enhanced phagocytosis in a dose-dependent manner. Leucine-enkephalin (Leu-Enk), methionine-enkephalin (Met-Enk), beta-neo-endorphin (beta Neo-End), DynA(9-17) and DynA(13-17) had no such activity. Alpha-Neo-endorphin (alpha Neo-End), dynorphin B (DynB), DynA(1-13) and DynA(6-17) enhanced phagocytosis less effectively than DynA. Naloxone did not inhibit the enhancement of phagocytosis induced by DynA. Unstimulated control phagocytosis was partially suppressed in Ca2+-free EGTA-containing solution and even in this solution DynA enhanced phagocytosis. However, the enhancement by DynA was suppressed in EGTA- and BAPTA-AM-containing Ca2+-free solution. The present study showed that enhancement of phagocytosis by DynA was independent of extracellular Ca2+ ([Ca2+]o) and dependent on intracellular Ca2+ ([Ca2+]i). The present results support DynA being one of the mediators from the nervous system that modulates the immune system.