The effect of obesity on gentamicin disposition was studied in 60 obstetric and gynecologic patients receiving treatment for Gram-negative infections. Thirty patients whose body weights were within 20 per cent of their ideal body weight were the control group. Thirty additional patients had body weights at least 30 per cent greater than ideal body weight and were the obese group. The two groups had similar ages, heights, ideal body weights (IBW), lean body weights (LBW), and elimination rates of gentamicin. The distribution volumes, expressed as liters or standardized to ideal body weight, lean body weight, or total body weight, were significantly different in the controls from those in obese patients. The distribution volume averaged (+/- S.D.) 0.19 +/- 0.06 1./kg in controls. The contribution of excess weight to additional drug volume averaged (+/- S.D.) 0.05 +/- 0.161./kg. Excess weight thus contributes less volume per kilogram than ideal body weight or lean body weight. A substantial interpatient variability existed in the measured distribution volume for all groups. Measuring serum concentrations and adjusting a patient's dosage regimen are imperative to ensure therapeutic serum concentrations.