There is considerable evidence from naturalistic studies that psychosocial stressors affect human immune function. To achieve control over factors that could bias naturalistic studies, laboratory stressors developed by cardiovascular researchers were tested to determine if they affected immune function. Thirty volunteer students were exposed to 20 minutes of mental tasks. Psychophysiological indices (heart rate, blood pressure, skin conductance) and subjective responses were monitored prior to, during, and 1-hour after the tasks, blood, samples for immunological analyses were also drawn at these times. Thirteen subjects who were not exposed to the tasks served as controls. Subjects exposed to the tasks showed increased levels of subjective distress and increased psychophysiologic responses (except diastolic blood pressure) during the tasks. Relative to controls, stressed subjects had reduced lymphocyte proliferative responses to classic T cell mitogens both immediateiy after and 1-hour after the tasks were found in whole blood cultures, although responses of isolated lymphocytes were not significantly affected. There were only marginal differences in whole blood mitogen responses for stressed subjects with low versus high autonomic reactions to the stressor. These results support an emerging view that the immune system is sensitive to brief stressors and that laboratory models may be useful for exploring stress-induced changes in immune function.