The effects of three beta-adrenoceptor blockers atenolol, indenolol and nadolol on myocardial mitochondrial ATPase (ATP: phosphohydrolase EC 3.6.1.3) activity were evaluated and compared with that of propranolol in guinea pig heart preparations. Propranolol and indenolol inhibited ATPase activity with IC50 values of 4.4 +/- 0.5 and 5.3 +/- 0.4 mM, respectively. In contrast, however, nadolol and atenolol markedly enhanced mitochondrial ATPase activity. Atenolol increased the enzyme activity by approximately 5, 240 and 950%, while nadolol enhanced it by 13, 280 and 2800% at 100 microM, 1.0 mM and 10.0 mM, respectively. The results indicate that these drugs exhibit two modes of interaction with the mitochondrial ATPase: inhibition by propranolol and indenolol and stimulation by atenolol and nadolol. The inhibitory actions are probably related to the membrane-stabilizing effects and therefore antiarrhythmic actions of the two drugs, while the stimulatory effects of atenolol and nadolol are probably a result of interactions with some component of oxidative phosphorylation or the respiratory chain.