In order to study the possible relation of hepatic lysosomal stability and enzyme release from the liver during stress, rats were sacrificed after swimming exercise, hypoxia, and epinephrine injections. Each of the stresses caused a decrease in hepatic lysosomal stability, an increase in plasma ornithine carbamoyltransferase (OCT), a liver specific enzyme, and increases in plasma creatine phosphokinase (CPK) and aspartate aminotransferase (AAT). With exercise, the decrease in lysosomal stability and the increase in OCT were first seen at one hour. The OCT increase preceded the lysosomal changes after hypoxia and followed the lysosomal changes after epinephrine injection. Prednisolone reduced the lysosomal and CPK (but not the OCT and AAT) changes with exercise, but had no effect with hypoxia or epinephrine injections. Adrenalectomy delayed the lysosomal changes and eliminated the increase in OCT after hypoxia and epinephrine. The varying time sequence of hepatic lysosomal changes and enzyme release with these stresses suggests that these two phenomena are not causally related.