The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given endotoxin, significant (P less than 0.05) increases were found in the serum concentration data (A, B, and CoS), and significant decreases were found in the apparent volume of distribution [Vd(area)] and in the volume of the central compartment (Vc). The alterations in gentamicin kinetics in the horses given endotoxin are believed to result from the decrease in Vc. This indicates that the extracellular fluid volume available for gentamicin distribution may be reduced by endotoxin.