We examined the effects of triphenyltin chloride (TPTCl) on the signal transduction in cells, especially the rise of cytosolic free calcium in fura-2-loaded neutrophils stimulated by N-folmyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). The peak concentration of cytosolic free calcium in neutrophils stimulated by FMLP (10(-7) M) after treatment with 4 mM EGTA was inhibited by TPTCl in a dose-dependent manner and completely blocked in the concentration range of 2.5 to 10 microM in the absence of extracellular calcium. TPTCl also had dose-dependent inhibitory effects on the superoxide anion production and the secretion of beta-glucuronidase in neutrophils stimulated by FMLP (10(-7) M). These results indicate that TPTCl is potent inhibitor of cytosolic free calcium mobilization in FMLP stimulation, associated with superoxide anion production and the secretion of beta-D-glucuronidase.