Cardiac dysfunction is a well known but poorly understood complication of iron overload. We have previously shown that cultured myocardial cells are able to assimilate large amounts of iron. In the present study, the effect of iron on the rate and amplitude of beating in monolayer cultures of rat ventricular myocytes was studied. Iron had negative chronotropic and inotropic effects, both reversible upon washout. The negative chronotropic effect developed earlier and could be reversed by adrenaline. The negative inotropic effect took longer to develop and was completely reversed by caffeine. Elevated [Ca++] also partially restored impaired contractility, while adrenaline or ouabain did not show any significant effect. These results indicate that iron toxicity in cultured heart cells impairs cellular function at both sarcolemmal and intracellular sites.