Tetanus antitoxin (TAT) was given to 39 horses (1500 IU) intramuscularly; 39 horses (1500 IU) subcutaneously; and 20 horses (25,000 IU) intravenously. Horses were evaluated for clinical evidence of hepatic disease before administration of TAT and on days 1, 2, 14, 60, and 120 after injection. Blood was collected on days 0, 1, 60, and 120 from 9 horses that received TAT by the subcutaneous or intramuscular route, and 5 horses that received TAT intravenously. Serum chemical analysis, which included measurement of total bilirubin concentration, and activity of gamma-glutamyltransferase, aspartate transaminase, and sorbitol dehydrogenase, was performed on the samples. All horses remained clinically normal throughout the 120-day postinjection period. On days 60 and 120 post-IM or SC administration, a statistically significant increase in mean gamma-glutamyltransferase serum concentration was observed compared with pretreatment concentrations, but these values did not exceed the normal reference interval. All other indices did not significantly increase throughout the study. Individually, only one horse had a slight elevation in SDH concentration on day 60 and 120. These findings suggest that administration of TAT rarely causes overt hepatic disease or persistent elevation of hepatic serum indices, regardless of the route of administration.