1. Methods - In order to verify that the antagonism of isoprenaline by bepridil was not exclusive to cardiac receptors, anesthetized dogs were subjected to a double isoprenaline stimulation (two 15 minute perfusions at a rate of 1 microgram . kg-1 . min . -1 separated by a 75 minute interval). Bepridil at 5 mg . kg-1 was injected intravenously 45 minutes before the second isoprenaline stimulation, and compared to propranolol (1 mg . kg-1), practolol (5 mg . kg-1) and perhexiline (2.5 mg . kg-1). In addition, bepridil (1 mg . kg-1 . min . -1) and perhexiline (0.5 mg . kg-1 . min-1) were also perfused intravenously, simultaneously with the second isoprenaline stimulation. Classical cardiovascular parameters (heart rate, left dP/dt max., arterial pressure, coronary artery flow) together with plasma free fatty acid levels (FFA) were monitored at intervals of 5 minutes throughout the study. 2. Results - The two isoprenaline stimulations caused non-statistically different increases in the various parameters. All the cardiovascular effects of isoprenaline were inhibited by propranolol, except for the increase in coronary flow. Likewise, the increased plasma FFA level fell by 82.7 +/- 4.2% (p = 0.003). The tachycardia and elevated left dP/dt max. were antagonised by practolol, which the increased FFA levels fell by 64.3 +/- 4.8% (p less than 0.01). The other parameters were not altered. No signficant effect was observed with perhexiline. Rapid I.V. infection of bepridil only decreased the isoprenaline. induced tachycardia (from 74 +/- 15.6 syst. Min.-1 to 57.3 +/- 12.7 syst. min.-1). Perfusion of bepridil considerably limited the tachycardia, while moderately reducing the increased contractility later on. However, it had no effect on FFA levels or the other cardiovascular parameters. 3. Discussion and conclusions - The results obtained with propranolol and practolol are consistent with the competitive B-blocking activity of both compounds. The lack of effect noted in this instance with perhexiline may be explained by the recent hypothesis whereby this compound acts on the presynaptic nerve endings of the cardiac pacemaker system and depresses the release of endogenous noradrenaline while unable to antagonise exogenous adrenergic stimulation. The dissociated effects of bepridil with regard to cardiac and lipolytic stimulation by isoprenaline, strongly suggest functional antagonism by both compounds at cardiac level alone. This antagonism is explained by the depressant effects of bepridil on Ca2+/Na+ slow inward currents, as shown previously in myocardial preparations.