Tiletamine and zolazepam, the two constituents of Telazol, were evaluated independently to determine which agent was responsible for the nephrotoxicity caused by Telazol in New Zealand White rabbits. Five rabbits were injected i.m. with 32 mg/kg of tiletamine, four animals received 7.5 mg/kg of tiletamine, and five rabbits received 32 mg/kg of zolazepam. Urinalysis was performed and blood urea nitrogen and serum creatinine were monitored for 7 days postinjection. In all five rabbits injected with the high dose of tiletamine, blood urea nitrogen and creatinine rose by 3 days postinjection and increased steadily throughout the week. By 4 days postinjection, urine protein and glucose were elevated and cellular and protein casts were present. No serum chemistry or urine abnormalities were detected in rabbits receiving low doses of tiletamine, zolazepam, or in the four control rabbits. All animals were euthanized and necropsied at 7 days postinjection. Histopathology showed severe renal tubular necrosis in all five rabbits injected with 32 mg/kg tiletamine. Mild nephrosis was present in three of four rabbits injected with 7.5 mg/kg of tiletamine. No lesions were present in the zolazepam-injected or control rabbits. The results of this study show that tiletamine is the constituent responsible for the nephrotoxicity of Telazol in rabbits. They further demonstrate that doses commonly used for anesthetic induction or restraint can produce renal lesions in rabbits.