Forty-five medical students were recruited to examine the effects of distress on the development of an immune response to the novel antigen, keyhole limpet hemocyanin (KLH). The subjects' level of distress was manipulated by immunizing them either at the time of an important viva voce examination (n=22) or during examination-free term time (n=23). This manipulation increased variance amongst the subjects, but the emphasis in this research was on individual distress as a predictor of immune function. In the group as a whole, the likelihood of developing DTH skin responses to KLH was reduced in the more distressed subjects (r=-.45; p=.002), independently of a number of behavioral (e.g., sleep disturbance) and demographic (e.g., sex) variables. Proliferation of T cells against KLH in vitro and the development of anti-KLH IgG antibodies were not related to levels of distress. Thus, cellular, rather than humoral, immune responses in vivo appear susceptible to the influence of distress. This immunization model provides the opportunity to further dissect the basis of these stress-immune pathways.