Pentoxifylline (PTX) has potential usefulness in HIV-seropositive patients due to its beneficial effects on renal function, its inhibitory effects on tumor necrosis factor alpha, and its vascular effects on microcirculatory disturbances. The present study prospectively evaluated the effects of multiple oral doses of PTX (400 mg three times daily for 12 weeks) on renal function in 11 HIV-seropositive patients compared with 14 control patients. Four of these patients had HIV-associated nephr-opathy, manifested by high urinary microalbumin outputs (72±56μg/min; mean±SD). Ambulatory 24-h urine collections were analyzed for creatinine, electrolytes, and immunological markers at weekly intervals for 12 weeks. Urine flow rates diminished to one-half baseline values by week 12; changes were related to both time and treatment sequences. There were significant decreases in creatinine clearances and electrolyte excretion rates over the study period that were not associated with treatment regimens. No differences were found in fractional electrolyte, uric acid, microalbumin, and neopterin excretion rates either between or within groups. One subject with high microalbumin excretion rates had a significant drop over the 12 weeks (133 to 4μg/min); the other 3 subjects had similar or elevated microalbumin outputs by the end of the study. Although well tolerated, therapeutic doses of PTX did not significantly affect renal function in HIV-seropositive patients.