The effect of zidovudine and didanosine on the cerebrospinal fluid (CSF) concentrations of neopterin was studied in 12 patients with human immunodeficiency virus type-1 (HIV-1) infection 3-12 months after initiation of antiretroviral therapy. Ten treatment periods on zidovudine and 7 on didanosine were analysed. The CSF concentrations of neopterin decreased by 63% (from 29.6 to 12.9 nmol/l, p < 0.01) during zidovudine but increased by 15% (from 22.6 to 25.9 nmol/l, not significant during didanosine treatment. The CSF monocytic cell count decreased during zidovudine but increased during didanosine treatment. The results suggest that zidovudine but not didanosine reduces intrathecal immunoactivation during HIV-1 infection.