Isovolumic contractions were imposed by intraventricular balloon in 39 isolated, blood-perfused canine hearts to investigate the effects of myocardial stretch on contractile force. After stabilization at 37 degrees C, left ventricular volume was increased so that end-diastolic pressure increased from 0 to 5 mmHg. After the immediate increase in developed pressure [DP; from 37 +/- 14 to 82 +/- 22 mmHg (means +/- SD)], there was a slow secondary rise in DP (97 +/- 27 mmHg) that peaked at 3 min. However, DP subsequently decreased over the next 7 min back to the initial value (84 +/- 25 mmHg). Light emission from microinjected aequorin (n = 10 hearts) showed that changes in intracellular calcium [3 min: 124 +/- 15% (P < 0.01); 10 min: 99 +/- 18% of baseline] paralleled DP changes. Increases in myocardial adenosine 3',5'-cyclic monophosphate (cAMP) content (n = 12) accompanied the secondary rise in DP. In contrast, the gradual elevation of DP after the stretch was not exerted during continuous beta-adrenergic stimulation by isoproterenol. Thus, in contrast to isolated muscle, stretch only transiently increases intracellular calcium and contractile strength in intact hearts. The findings of changes in cAMP and abolition of the phenomena by beta-stimulation suggest that a primary stretch-mediated influence on cAMP metabolism may underlie these phenomena.