Risk factors for the development of auditory toxicity in patients receiving aminoglycosides were determined from the analysis of 135 patients enrolled in three prospective, randomized, double-blind clinical trials of gentamicin, tobramycin, and amikacin. Auditory toxicity, defined as a decrease in auditory acuity of greater than or equal to 15 dB, occurred in 30 patients (22.3%). Patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, and had, on the average, a higher temperature (P less than 0.05). Using stepwise discriminant analysis, we selected these factors with liver dysfunction and the serum urea nitrogen:serum creatinine ratio in a function that accurately discriminates between toxic and nontoxic patients. Factors not adding significantly to the predictive accuracy of the equation were plasma aminoglycoside levels, aminoglycoside type, furosemide use, diabetes, age, sex, renal function, initial auditory acuity, hematocrit value, and shock. This analysis may be important both for determining the pathophysiology of auditory toxicity and for the prognostic stratification of patients receiving aminoglycosides in clinical trials.