Platelet-derived growth factor (PDGF) produced an almost complete block of the increase in intracellular free Ca2+ concentration ([Ca2+]i) in Swiss 3T3 fibroblasts caused by the Ca2(+)-selective ionophores 4-bromo-A23187 and ionomycin, and by the volatile anesthetic agent halothane. The effect of PDGF was similar to the decreased [Ca2+]i response to Ca2(+)-ionophores produced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. There was no effect of PDGF or PMA on the acute or delayed toxicity of the Ca2(+)-ionophores to Swiss 3T3 cells, suggesting that the increase in [Ca2+]i is not the direct cause of toxicity of these agents.