The absorption and disposition of ethambutol was examined in six rabbits in a three-way crossover study. Each rabbit received 45-mg/kg doses of ethambutol in three treatments: one intravenous injections and two oral solutions, ethambutol alone and ethambutol in the presence of aluminum hydroxide (40 mg/kg). Half-lives of ethambutol ranged from 2.26 to 5.20 h when administered alone and 2.18 to 4.00 h when coadministered with the antacid; the difference was not significant (p greater than 0.3). Mean clearance after the oral administrations (189.2 mL/min/kg) was significantly greater than the mean intravenous clearance (43.7 mL/min/kg) (p less than 0.01), suggesting a first-pass metabolism of ethambutol when administered nonparenterally to rabbits. The volume of distribution ranged from 5.5 to 17.8 L/kg, suggesting an extensive distribution of ethambutol outside the central compartment and, possibly, a localized deposit within the body tissues. Mean bioavailability of ethambutol was approximately 28% and was not affected by the presence of aluminum hydroxide. The rate of ethambutol absorption, however, was slightly delayed by the antacid.