ObjectiveTwo important determinants of physiological stress responses have been identified, uncontrollability of the stressor and amount of effort involved in coping with the stressor. In the present experiment, we tried to identify the specific contributions of effort and uncontrollability to immune system responses to stress.MethodsIn a 2 x 2 design, effort and uncontrollability were manipulated independently of each other. Subjects participated in one of four experimental conditions, and their endocrine, immune, and sympathetic nervous system responses to the task were assessed.ResultsEffort had a stimulating effect on enumerative immunological parameters (CD8+and CD16+cells) and on natural killer cell activity. The effect occurred immediately after the stressor and was transient. Regression models indicated that this effort effect may have been mediated by activation of the sympathetic nervous system. Uncontrollability influenced in vitro production of the cytokine interleukin-6, leading to decreased production 15 and 30 minutes after the stressor. Uncontrollability also led to an increased level of cortisol, but no evidence was found that the decrease in cytokine production was mediated by cortisol release.ConclusionThe results suggest that two major stressor characteristics, effort and uncontrollability, may have differential effects on the immune system.