We have previously shown that supplementation of inflammation-inducing zymosan with a high dose ofmorphine inhibits peritoneal influx ofleukocytes in Swiss, C57C3H, Balb/c, and C57BL/6 strains but not in CBA mice. We have also reported that the different pattern of the response to morphine treatment might be, at least partially, due to the inter-strain differences in the peritoneal mast cell (P-MC) number (high in CBA mice versus other strains) and P-MC specific features (high sensitivity to degranulation upon morphine treatment in CBA mice). The aim of the present study was to investigate the mechanism of morphine action on P-MC in CBA mice. In particular, the effects of morphine on the proliferation and migration of P-MC in CBA mice with ongoing zymosan-induced peritonitis modulated by morphine were studied. Morphine alone acted as a strong chemoattractant for P-MC of CBA mice and this effect was opioid receptor-independent. Moreover, flow cytometric analysis showed that i.p. morphine injection induced significant proliferation of P-MC in CBA mice. Therefore, we conclude that the lack of anti-inflammatory effects of morphine during peritonitis in CBA mice might result not only from a unique sensitivity of CBA mast cells to morphine-induced degranulation but also from the fact that mast cell numbers increase at the inflammatory focus. The latter might be due to morphine-induced mast cell proliferation and/or migration.