Intraperitoneal injection of ketamine (100 mg/kg body weight) significantly reduces the levels of cholecystokinin (CCK), somatostatin (SRIF), and substance P (SP)-like immunoreactivity in various regions of rat brain. No significant change in thyrotropin releasing hormone (TRH)-like immunoreactivity was observed. Neuropeptide systems may be involved in the neuropharmacologic effects of ketamine.