Risk factors for nephrotoxicity in patients treated with aminoglycosides were determined from the case records of 214 patients in two prospective, randomized clinical trials of gentamicin and tobramycin. Nephrotoxicity, defined as a 50% or greater fall in calculated creatinine clearance, developed in 30 patients (14.1%). Patients with nephrotoxicity had higher initial calculated creatinine clearances, were more often women, and were more likely to have liver disease. Using stepwise discriminant analysis, these factors were selected with the initial 1-hour post-dose aminoglycoside level, patient age, and shock. An equation was generated that was accurate in discriminating between patients with and without nephrotoxicity when validated in an independent population. Factors that did not add significantly to the equation were diabetes, dehydration, serum bicarbonate, bacteremia, urinary tract infection, gentamicin or tobramycin use, duration of therapy, total aminoglycoside dose, or the use of clindamycin, furosemide, or cephalothin.