The action of the calcium antagonists nifedipine, bepridil, diltiazem and of an alpha adrenergic antagonist, prazosin, was studied on Ca2+ uptake and energy supply (i.e. oxidative phosphorylation) of sheep heart mitochondria. In order to appreciate an inhibition, uncoupler like, of the Ca2+ influx, a comparative study was made with DNP. The Ca2+ uptake was inhibited, at the concentrations tested, (less than or equal to 10(-3) M), only by bepridil, nifedipine and DNP: a 2.5.10(-4) M concentration of these drugs brought an inhibition of 95%, 65% and 100% respectively. The inhibition was accompanied by a decrease of the ADP:O ratio and the RCI except with nifedipine. It is suggested that bepridil could act more as an inhibitor-uncoupler and nifedipine as an inhibitor of the Ca2+ uptake uniporter; both leading to a decrease of the mitochondrial participation in the regulation of the cellular homeostasis. This phenomenon could contribute to the known clinical properties of bepridil and nifedipine.