Foveal and conventional full field pattern-shift visual evoked potentials (f-VEPs and c-VEPs) were recorded bilaterally in 100 HIV seropositive homosexual men (HIVs) and in 40 age-matched healthy controls. In HIVs, both f-VEPs and c-VEPs revealed a significant mean increase in P100 latency (p < 0.001). In stage WR2 early conduction changes were detected in 17% of the stimulated eyes by f-VEPs and in 3% by c-VEPs. In patients with CD4 cell counts below 100/microliters a 33% reduction in the mean c-VEP amplitude was found (ANOVA p < 0.01). Multivariate analyses (MANCOVA) revealed that CD4 cell depletion was independently associated with lower (p < 0.01) and zidovudine treatment with higher c-VEP amplitudes (p < 0.05). Also patients with severe CD4 cell depletion showed a trend towards higher c-VEP amplitudes (p = 0.09) and lower f-VEP latencies (p = 0.08) after long lasting zidovudine treatment (Kruskal-Wallis test). Our data suggest that f-VEPs are a sensitive measure of subclinical optic fiber dysfunction in early HIV-1 infection and that axonal loss of optic fibers emerges with manifest immune deficiency. The inverse correlation of VEP changes and zidovudine treatment merits further studies on the question, whether inhibition of HIV replication may preserve visual pathway function.