Relaxation of spontaneously contracting single rat cardiac cells with an effective sarcoplasmic reticulum was shown to be sensitive to load, as previously described for intact mammalian ventricular cardiac muscle. Caffeine and tetanic stimulation could modify load-dependent relaxation in intact papillary muscle from cat or rat into a load-insensitive relaxation. Although such load dependence was demonstrated to be normally absent in frog ventricular cardiac muscle, in the present study it could also be made moderately manifest under specific conditions, e.g., high calcium, low sodium, or ouabain. The appearance of load dependence during relaxation in cardiac muscle thus emphasizes the presence of an effective sarcoplasmic reticulum.