Increased serum enzyme activity after exercise was first reported in 1958; subsequent studies have established that many factors determine the degree to which the serum activities of a variety of enzymes increase during and after exercise. The serum activities of those enzymes found especially in muscle, particularly creatine kinase, increase in proportion to the intensity and duration of the preceding exercise, peaking 24 hours after exercise; the effect of duration is dominant, so that the highest postexercise serum enzyme activities are found after very prolonged competitive exercise such as ultradistance marathon running or triathlon events. Weight-bearing exercises which include eccentric muscular contractions such as bench stepping and downhill running induce the greatest increases in serum enzyme activities; serum enzyme activities increase very little even after prolonged participation in those non-weight-bearing activities such as swimming and cycling which do not include eccentric muscular contractions. Prolonged (greater than 2 hours) daily training or competition in weight-bearing activities produces chronically elevated serum enzyme activities. Serum enzyme activities increase more with exercise in males, Blacks and the untrained than they do in females, Whites and the trained, respectively; age does not appear to influence the degree to which serum enzyme activities increase with exercise. There is a remarkable individual variability in the degree to which serum enzyme activities increase with exercise; a 50-fold difference in post-race serum creatine kinase activities has been found in healthy and equally trained athletes completing the same 90km ultramarathon footrace. The biochemical explanation for this degree of individual variability is not currently understood; possibly persons who show abnormally large increases in serum enzyme activities with exercise may have as yet unrecognised subclinical myopathies. No circadian rhythms have been identified for serum enzyme activities; activities rise during the day because of increased physical activity. The rise in serum enzyme activities is greater after exercise at altitude or in the heat than after equivalent exercise at sea level or in the cold. The most likely explanation for the increased serum enzyme activities that follow prolonged weight-bearing activities that also cause marked muscle soreness, is myofibrillar damage in particular sarcomeric Z-disk disruption.(ABSTRACT TRUNCATED AT 400 WORDS)