This study used a year-long prospective design to assess linkages among distress, immunity, and illness. Serial blood samples were collected from 40 first-year medical students at the first, third, and fifth examination periods, as well as 1 month before each. There were significant decrements in the production of gamma-interferon by concanavalin A-stimulated lymphocytes obtained at the time of examinations. Antibody titers to Epstein-Barr virus (EBV) increased during examination periods, suggesting reactivation of latent EBV and therefore poorer cellular immune control of latent virus. We obtained data that suggest that T-cell killing by memory T lymphocytes of EBV transformed autologous B lymphocytes also declined during examination periods. The activity of a lymphokine, leukocyte migration inhibition factor, normally suppressed during recrudescence of herpes simplex virus type 2 infections, was altered during examination periods and an increase in both plasma and intracellular levels of cyclic AMP associated with examination stress was observed. An increase in the incidence of self-reported symptoms of infectious illness was also associated with examination periods. The data support the linkage between stress-related immunosuppression and health.