BACKGROUND AND AIM: Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. As peritoneal mast cells (pMCs) are much more numerous in CBA mice than in SWISS mice, therole of pMCs in morphine-modulated zymosan peritonitis is compared in CBA and SWISS males. METHODS: pMCs were treated in vitro with morphine or C48/80 for comparison of histamine release. In vivo accumulation of leukocytes and histamine in peritoneal exudate were recorded after intraperitoneal injection with morphine, zymosan, or zymosan plus morphine. RESULTS AND CONCLUSION: Morphine induces histamine release by pMCs from CBA mice but not SWISS mice. In vivo morphine-induced peritonitis is stronger in CBA mice than SWISS mice. Corollary, morphine anti-inflammatory effects on zymosan peritonitis are reversed in CBA mice by its pro-inflammatory action through CBA pMCs.