Study Objective. To compare the results of an artificial neural network approach with those of five published creatinine clearance (Cl-cr) prediction equations and with the measured (true) Cl-cr in patients infected with the human immunodeficiency virus (HIV). Design. Six-month prospective study. Settings. Two university medical centers. Patients. Sixty-five HIV-infected patients: 18 relatively healthy outpatients and 47 inpatients. Interventions. All subjects had urine collected for 24 hours to determine Cl-cr. Measurements and Main Results. The 16 input variables were age, ideal body weight, actual body weight, body surface area, height, and the following blood chemistries: sodium, potassium, aspartate aminotransferase, alanine aminotransferase, red blood cell count, platelet count, white blood cell count, glucose, serum creatinine, blood urea nitrogen, and albumin. The only output variable was Cl-cr. A training set of 55 subjects was used to develop the relationship between input variables and the output variable. The trained neural network was then used to predict Cl-cr of a validation set of 10 subjects. Mean differences between predicted Cl-cr and actual Cl-cr (bias) were 4.1, 28.7, 29.4, 26.0, 31.8, and 55.8 ml/min/1.73 m(2) for the artificial neural network, Cockcroft and Gault, Jelliffe 1,Jelliffe 2, Mawer et al, and Hull et al methods, respectively. Conclusion. The accuracy of predicting Cl-cr in subjects with HIV infection by the artificial neural network is superior to that of the five equations that are currently used in clinical settings.