Chelerythrine, a potent inhibitor of protein kinase C (PKC), was evaluated for its effect on inositol phosphate (IP) metabolism in newborn rat cardiomyocytes in culture. In a first step, we evaluated the effect of chelerythrine on IP accumulation in basal conditions. For a 10–4 M dose, 5‐phosphatase activity (which dephosphorylates IP3 into IP2) was completely blocked and we observed a large increase in IP accumulation limited to IP2 without any increase in IP3, strongly suggesting that chelerythrine at this dose modifies IP metabolism. At a lower dose (10–5 M) of chelerythrine, which did not modify IP accumulation and 5‐phosphatase activity in basal conditions, the response to angiotensin II stimulation was completely abolished by the addition of chelerythrine. We conclude thus that chelerythrine, even at 10–5 M, interacts markedly with IP metabolism, and caution should be exerted when interpreting the results obtained with this drug, which is still currently used at this dose.