The purpose of this study was to test the hypothesis that loading patterns (i.e., loading sequence, total load, and preload) modulate the relaxant effects of isoproterenol. The effects of isoproterenol (10(-6) M) on peak rate of force decline (-dF/dt) were studied in rat left ventricular papillary muscle (n = 24) with respect to two sequences of relaxation: the classical, isotonic-isometric sequence, in which tension fall occurs at initial muscle length, and the physiological, isometric-isotonic sequence, in which tension fall occurs at end-systolic muscle length. The influences of muscle load and initial length were accounted for in the evaluation of relaxation rate by plotting -dF/dt against the entire range of loads both at preload = maximum length (Lmax) and 90% Lmax. The main results are the following: 1) in the classical, isotonic-isometric sequence of relaxation, and whatever the preload, the magnitude of the relaxant effect of isoproterenol increased with load; 2) after reversal into the physiological, isometric-isotonic sequence of relaxation, the relaxant effect of isoproterenol behaved independently of load level in muscle preloaded at Lmax; 3) conversely, in muscle preloaded at 90% Lmax and relaxing according to the physiological sequence, the relaxant effect of isoproterenol increased with load; and 4) the peak relaxant effect of isoproterenol was proportionally higher in the physiological sequence of relaxation than in the classical one and occurred at a similar level of load, whatever the loading sequence and whatever the preload level. Our results indicate that loading patterns finely modulated the relaxant effects of isoproterenol and that muscle length, both before the contraction phase and at the onset of relaxation phase, influenced the effects of isoproterenol on myocardial relaxation rate.