This study was a 19-week prospective conducted to determine the effectiveness of a self-hypnosis/relaxation intervention to relieve symptoms of psychological distress and moderate immune system reactivity to examination stress in 35 first-year medical students. Twenty-one subjects were randomly selected for training in the use of self-hypnosis as a coping skill and were encouraged to practice regularly and to maintain daily diary records related to mood, sleep, physical symptoms, and frequency of relaxation practice. An additional 14 subjects received no explicit training in stress-reduction strategies, but completed similar daily diaries. Self-report psychosocial and symptom measures, as well as blood draws, were obtained at four time points: orientation, late semester, examination period, and postsemester recovery. It was found that significant increases in stress and fatigue occurred during the examination period, paralleled by increases in counts of B lymphocytes and activated T lymphocytes, PHA-induced and PWM-induced blastogenesis, and natural killer cell (NK) cytotoxicity. No immune decreases were observed. Subjects in the self-hypnosis condition reported significantly less distress and anxiety than their nonintervention counterparts, but the two groups did not differ with respect to immune function. Nevertheless, within the self-hypnosis group, the quality of the exercises (ie, relaxation ratings) predicted both the number of NK cells and NK activity. It was concluded that stress associated with academic demands affects immune function, but immune suppression is not inevitable. Practice of self-hypnosis reduces distress, without differential immune effects. However, individual responses to the self-hypnosis intervention appear to predict immune outcomes.