The effect of nephrectomy on the disposition of ethambutol was investigated in seven adult mongrel dogs: five were nephrectomized and two served as the control. Each dog was intravenously administered 500 mg ethambutol, followed by blood sample collection for 12 h. Total urine was collected over 24 h from the normal control dogs. Ethambutol contents in plasma and urine were assayed by a GC method. The nephrectomized group and the control group exhibited differences in the following pharmacokinetic parameters: half-life, 5.0 versus 4.1 h (significant at p less than 0.1); total body clearance, 8.4 versus 13.2 mL/min/kg (significant at p less than 0.1); and volume of distribution, 2.7 versus 3.8 L/kg (significant at p less than 0.1). Comparison of pharmacokinetic parameters among rabbits, dogs, and humans revealed distinct interspecies differences with regard to total body clearance, renal clearance, volume of distribution, and fractional renal excretion. One comparable parameter shared by all species is the beta-phase half-life.