Three healthy young men participating in phase 1 clinical vaccine trials had unexplained increases in their serum transaminase levels. Retrospective analysis indicated that these volunteers had participated in strenuous physical training 2-5 days prior to the noted elevations. The pattern of serum enzyme elevations, initially thought to be consistent with hepatic injury, were associated with parallel increases in creatine phosphokinase. One individual consented to repeat his exercise regimen. This was followed by a recurrence of the same pattern of increases in serum enzymes, including creatine phosphokinase. Thus, in trials where serum enzymes will be measured, it may be prudent to encourage subjects to refrain from increasing their activity above that which they normally perform.