In recent years the management of human immunodeficiency virus (HIV)-positive individuals has been based on highly active antiretroviral therapy (HAART) comprising a combination of nucleoside analogues or the combination of these agents with protease inhibitors. The aim of the present study was to describe the prevalence of oral lesions in a cohort of 103 HIV-seropositive patients on HAART, to compare these data with the prevalence of lesions prior to HAART and to correlate these finding with the immunologic data. A total of 103 HIV-seropositive patients on HAART were selected. Oral lesions associated with HIV infection and immunological parameters were registered. On re-examination 6 months after the first evaluation, 61/103 patients were available. Comparing the prevalence of oral lesions before and after the onset of HAART, the number of oral lesions was significantly lower (P=0.001). The number of CD4+ cells increased and the viral load decreased significantly after initiation of HAART (P=0.001 and P= 0.0001). On re-examination 6 months later, the prevalence of lesions again decreased significantly (P=0.001). The immunological benefits of HAART may prevent HIV-associated oral lesions in patients with advanced HIV disease. Our results showed that oral manifestations decrease on HAART, but in four patients the immunological effects of therapy did not provide sufficient protection against human papillomavirus (HPV)induced lesions.