In an uncontrolled study, vancomycin pharmacokinetics were determined in four normal (total body weight [TBW], 65.9 to 89.1 kg) and six morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese (TBW, 111.4 to 226.4 kg) subjects. The morbidly obese subjects were investigated 3 to 4 h after gastric bypass surgery. Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW. The mean terminal half-life and volume of distribution values were significantly different between the two groups. Strong correlations were found between TBW and both volume of distribution (correlation coefficient, 0.943) and total body clearance (correlation coefficient, 0.981). There results implied that TBW should be used to calculate vancomycin doses for morbidly obese patients. This was supported by the finding that there was no significant difference in the daily dose (in milligrams per kilogram per day) required to produce an average steady-state concentration of 15 micrograms/ml in the two groups (23.4 +/- 1.5 mg/kg per day for normal weight subjects and 24.0 +/- 3.4 mg/kg per day TBW for the postsurgery morbidly obese subjects). Therefore, the morbidly obese required higher total doses (in milligrams per day) than did normal weight subjects to achieve the same mean steady-state concentrations. In addition, normal weight and morbidly obese subjects had similar volumes of the central compartment (7.7 and 6.4 liters, respectively). To avoid high transient peak concentrations which would occur when obese patients are given larger total doses (in milligrams per day), maintenance doses may be given at more frequent intervals. The shorter mean terminal half-lives observed in morbidly obese patients allows more frequent dosing without excessive accumulation.