Previous studies of psychopathological populations and populations challenged by significant life events have shown that high levels of anxiety and depression are associated with impaired cellular immunity. However, less is known about the sources and psychoimmunological relevance of subclinical variations in distress in healthy populations faced with typical levels of life stress. In the present study, we examined the relations of state distress to T-cell function and in vivo cytokine levels in 40 male college freshmen on two occasions. In addition, we assessed the possible contribution of dispositional determinants of distress to immune-related differences in mood. Relative to characteristically less anxious subjects, subjects who were characteristically more anxious (but subclinically anxious) had more anxious mood and had significantly lower lymphocyte proliferative responses to the mitogen concanavalin A (Con A) as well as lower levels of circulating interleukin-1 beta. In addition, subjects with more negative attributional styles for bad events exhibited reduced Con A-stimulated T-cell responses and lower levels of circulating interleukin-2. Finally, subjects who were more depressed (but subclinically depressed) also had reduced blastogenic responses. Individual differences in cortisol and beta-endorphin were not shown to mediate these relationships. The present study provides evidence that dispositionally related variations in distress in psychiatrically healthy, relatively unstressed college males have immunological correlates that suggest altered T-cell and macrophage activity.