Relaxation of isolated mammalian cardiac muscle is known to be influenced by loading conditions, but the mechanical determinants of relaxation velocity in the intact heart are not well defined. Accordingly, we measured the time constant (T) of left ventricular (LV) isovolumic pressure decline during descending and ascending thoracic aorta cross-clamp (single beat interventions) and during constriction of the descending and ascending thoracic aorta (5-min steady-state experiments). The single-beat interventions which acutely increase systolic pressure and length and decrease shortening resulted in a prolonged (increased) T. In steady-state interventions, descending aorta constriction produced an increase in T, while ascending aorta constriction produced a decrease in T. In these studies, the mean arterial pressure in the arch of the aorta increased in the descending constriction experiments and decreased in the ascending constriction experiments, and thus baroreceptor reflex activity may have been responsible for the observed differences. These studies confirm the dependency of LV relaxation on systolic pressure and suggest that other factors are superimposed on the load-dependency of relaxation in the intact heart.