Rat serosal mast cells were challenged with compound 48/80 or calcium ionophore A23187 and the effect of staurosporine, a new inhibitor of protein kinase C, on histamine release from the cells was investigated. Histamine release induced by compound 48/80 or calcium ionophore A23187 was inhibited by staurosporine in a concentration-dependent manner and 0.1 and 1 microM staurosporine inhibited the histamine release significantly. The inhibitory effect of K-252a, another novel protein kinase C-inhibitor, was significantly higher than that of staurosporine on calcium ionophore A23187-induced histamine release. These results suggest that protein kinases will be involved in the process during mediator release from rat serosal mast cells.