Noncirrhotic portal hypertension (NCPH) represents a relatively infrequent group of conditions that causes portal hypertension in the absence of cirrhosis. An association between NCPH and patients infected with human immunodeficiency virus (HIV) has been reported. Six consecutive patients with HIV infection and NCPH were the subject of this series. Case histories, including medication lists, liver biopsy and laboratory data were reviewed. Age at diagnosis was 43 +/- 3 years (range, 37-47). Liver disease was diagnosed 12 +/- 4 years (range, 8-18) after initiation of antiretroviral therapy (ART). All patients developed esophageal varices, 5 patients presented at least one bleeding episode and 2 required TIPS. Serum liver tests showed a mean total bilirubin of 1.4 +/- .7 mg/dL (range, .5-2.5) and INR was 1.2 +/- .14 (range, 1.0-1.4). CD4 count was 326 +/- 124 cells/mL (range, 198-467) and all patients presented HIV viral load < 75 copes/mL. Didanosine (ddl) was the most common ART drug being used by 4 patients. Portal vein thrombosis was diagnosed in 2 patients. Hepatic portal sclerosis (HPS) alone was observed in 1 patient, nodular regenerative hyperplasia (NRH) alone in 2 patients and combined HPS/NRH in 3 patients. In conclusion, NCPH should be included in the differential diagnosis of HIV-individuals presenting with clinical manifestations of portal hypertension and well preserved liver synthetic function. Prolonged exposure to ART, specially ddl, can play a pathogenic role. Rarely, liver synthetic function is sufficiently severe to warrant liver transplantation.