The alpha 1-agonist phenylephrine (5 microM) induces an increase in the free cytosolic Ca2+ concentration, followed by repetitive transients of the cytoplasmic Ca2+ concentration, in single Fura-2 loaded hepatocytes. The tumor promoting, hypolipidemic drug nafenopin suppressed the cellular Ca2+ response to phenylephrine. The effect of nafenopin on the Ca2+ increase and Ca2+ oscillations was largely prevented by the specific protein kinase C inhibitor Gö 6976. This finding suggests involvement of protein kinase C in the action of nafenopin on phenylephrine induced Ca2+ mobilization.