Summary Cats pretreated with methiothepin and then injected intramuscularly with a minimum anesthetic dose of ketamine become anesthetized sooner, sleep longer, and take longer to recover than control animals. Instead of muscle tonus and limb rigidity, muscle flaccidity is seen. Limb-withdrawal and jaw reflexes disappear. Respiration loses its irregular, apneustic character. These effects are dose-dependent and are not produced by a sedative dose of chlorpromazine or pimozide. Pimozide prevents the sporadic stimulus-induced paw twitching typical of ketamine, but neither methiothepin nor chlorpromazine do this. The results suggest serotonergic mechanisms may function to partly offset or adapt to the depressant effects of ketamine, to mediate ketamine catalepsy, and to produce respiratory irregularity and apneusis. Stimulus-induced muscle twitching due to ketamine may be a dopaminergic phenomenon.