The positive role of highly active anti-retroviral therapy (HAART) in reducing opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients is well known. However, case reports from around the world have demonstrated that some patients seem to suffer a paradoxical deterioration of health as their immune function improves with treatment. This phenomenon has been called immune restoration inflammatory syndrome (IRIS). In northern Thailand, GPO-vir (Stavudine-D4T + Lamivudine-3TC + Nevirapine-NVP) has been promoted for the treatment of AIDS patients since April 2002, in accordance with the Government Pharmaceutical Organization's guidelines. However, the incidence rates of IRIS affecting nervous system (NIRIS) and non-NIRIS in comparison with the previous incidence of AIDS-defining disease have not been reported. We conducted a retrospective study to review the incidence of NIRIS and non-NIRIS in AIDS patients treated with GPO-vir in Chiang Mai University Hospital, Thailand, between May 2002 and April 2004. We compare these incidence rates with the incidence rates of neurological complications in the pre-HAART era. Altogether 506 AIDS patients were treated with GPO-vir during the specified period. The overall incidence of NIRIS, including progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis and cytomegalovirus (CMV) retinitis, was lower than the previous incidence of AIDS-defining disease in the pre-HAART era. However, the incidence of ischemic stroke, hemorrhagic stroke and primary central nervous system (CNS) lymphoma had increased.