Urinary neopterin levels are raised with a high incidence in all risk groups for AIDS. Neopterin elevations reflect activated cellular immunity in risk group members, in some cases independently of LAV/HTLV-III infection. Moreover, we are able to show that in patients receiving multiple blood transfusions at least a transient challenge of cell-mediated immunity occurs, which is indicated in part by increasing neopterin levels. We conclude that neopterin levels are a reliable index for assessment of susceptibility for AIDS when infection with LAV/HTLV-III occurs. Activated status of cell-mediated immunity might predispose infected persons to an overwhelming infection and secondary spreading of LAV/HTLV-III, thus leading to the development of full-blown AIDS or ARC. As a consequence of these observations, T-cell-stimulatory actions and agents should intentionally be avoided. Treatment of AIDS patients with immunosuppressants should be examined. The success of therapeutic regimens should be monitored by measurement of neopterin levels.