Rats were exposed to a 3-wk regimen of chronic normobaric hypoxia, with or without almitrine treatment. Chronic hypoxia led to a significant rise in the right ventricular mass and lengthened the action potential duration (APD) in right ventricle and in nonhypertrophied left ventricle. Hypertrophy and APD lengthening were significantly enhanced by almitrine. The classical acute hypoxia-induced shortening in APD was much larger in hypoxia-adapted hearts. In these hearts, almitrine treatment almost completely prevented such shortening, while the acute hypoxia-induced decrease in cardiac contraction was similar with or without almitrine. It is concluded that APD lengthening during chronic hypoxia can occur independently of ventricular hypertrophy. The similar directional effects of almitrine and chronic hypoxia on APD support the hypothesis of an energy-linked phenomenon. The dissociation of the almitrine effect on APD and contractility is in accordance with the view of a cellular energy compartmentation.