Arterial lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) levels were measured at rest and during exercise, before and after a conditioning program, in 11 patients with coronary artery disease. Myocardial A-V differences of LDH were also obtained during exercise in 5 patients. No significant elevation of the arterial myocardial LDH fraction (LDH-1) or of CPK was seen during exercise. In the untrained subjects, arterial LDH-5 concentration rose during exercise before training. This rise was attenuated by the training program. Myocardial production of LDH, its isoenzymes, or CPK was not found, even during exercise producing anginal pain. These data suggest that tolerable exercise does not cause significant myocardial injury. Evidence for a peripheral effect of conditioning is deduced from changes in LDH-5 response to exercise.