We have demonstrated that a 72-kDa non-receptor-type protein-tyrosine kinase (p72syk) was co-immunoprecipitated with membrane IgM in digitonin lysates of porcine tonsillar cells and was rapidly activated following the engagement of membrane IgM. This activation was occurred within 5 s, even in the presence of EGTA and 5,5'-dimethyl-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid as extracellular and intracellular Ca(2+)-chelating agents, respectively, as well as in the presence of the protein-kinase-C inhibitor, H-7. Additionally, genistein, a potent protein-tyrosine kinase inhibitor, was capable of reducing both IgM-stimulated Ca2+ mobilization and p72syk activation in a dose-dependent manner. These results indicate that p72syk is physically associated with the B-cell-antigen receptor, participating in antigen-mediated signal transduction in both a Ca(2+)-independent and protein-kinase-C-independent manners.