The aim of these studies was to determine whether phosphodiesterase inhibition by enoximone is able to regulate differentially beta 1- and beta 2-adrenoceptor (AR)-mediated inotropic effects. Strips of human right atrial myocardium were stimulated with noradrenaline plus ICI 118,551 (selective beta 1-AR stimulation) or adrenaline plus CGP 20,712A (selective beta 2-AR stimulation). Concentration-effect curves were determined in the absence or presence of enoximone. Enoximone alone was shown to produce dose-related positive inotropic effects. In tissues from beta 1-blocker-treated patients, enoximone potentiated the responses to both beta 1-AR and beta 2-AR stimulation. There was a fall in -log EC50 (mol/l) of 0.7 +/- 0.2 (mean +/- SEM; n = 6) for beta 1-AR stimulation and of 0.6 +/- 0.1 (n = 10) for beta 2-AR stimulation. The potentiation of beta 2-AR responses in non-beta-blocker-treated patients was similar with a fall in -log EC50 (mol/l) of 0.5 +/- 0.1 (n = 6). The extent of potentiation was not significantly different between beta 1-AR and beta 2-AR stimulation, nor between beta 1-blocker-treated patients and non-beta-blocker-treated patients. Further experiments showed that the potentiation by enoximone of the effects of catecholamines was unaltered by diazoxide (n = 6). Enoximone thus causes positive inotropic effects and potentiates the effects of catecholamines acting through both beta 1- and beta 2-AR. These actions are consistent with inhibition of cyclic AMP hydrolysis. The potentiation of the effects of catecholamines by phosphodiesterase inhibition appears unaltered by prior patient therapy with beta 1 blockers.