The effects of increasing doses of two inotropes, isoproterenol and calcium chloride (CaCl2), on left ventricular regional myocardial function and isovolumic relaxation were studied in six anesthetized sheep. After baseline data, CaCl2 was given as intravenous boluses to yield doses of 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 160 mg/kg. After a second series of baseline data were obtained, constant infusions of isoproterenol were begun with doses of 0.025 micrograms/kg/min, 0.05 micrograms/kg/min, 0.1 micrograms/kg/min, 0.2 micrograms/kg/min, and 0.4 micrograms/kg/min. During each stage of the protocol with both inotropes, data were recorded during acute constriction of the descending thoracic aorta. Left ventricular relaxation was assessed by analysis of peak negative left ventricular (LV) dP/dt and the time constant of isovolumic left ventricular relaxation (Trelax). Regional myocardial function showed little change in either apical or basal segments until high doses of the inotropes. Peak negative LV dP/dt significantly changed from baseline (775 +/- 60 mmHg/s) with 0.2 micrograms/kg/min (1780 +/- 400 mmHg/s, P < 0.05 v baseline) and 0.4 micrograms/kg/min (2,220 +/- 380 mmHg/s, P < 0.05 v baseline) of isoproterenol, and was unchanged by CaCl2. Trelax was significantly decreased by all doses of isoproterenol, whereas only one dose of CaCl2 decreased Trelax. Trelax was increased with afterloading and this effect was altered by isoproterenol. It is concluded that isoproterenol hastens, whereas CaCl2 does not alter, left ventricular relaxation. This may reflect beta-adrenergic modulation of calcium fluxes during isovolumic relaxation.