The effects of a wide range of doses of systemically administered cysteamine were studied on locomotor behavior, passive avoidance memory, cortical and cerebrospinal fluid somatostatin-like immunoactivity and cortical levels of dopamine and norepinephrine. High doses of cysteamine (200 and 250 mg/kg s.c.) led to sustained locomotor activation. Doses of 150 mg/kg and above resulted in head and neck tremor and increased defecation. When cysteamine was administered immediately following the acquisition of a passive avoidance response, doses of 50 mg/kg and above resulted in significant attenuation of passive avoidance retention test performance. Cysteamine in doses of 50 mg/kg and above depleted cortical somatostatin-like immunoactivity by approximately 50%. The depletion of cortical somatostatin-like immunoactivity was accompanied by a rapid rise in somatostatin-like immunoactivity in cerebrospinal fluid. In addition to the depletion of somatostatin-like immunoactivity, high doses of cysteamine (150 mg/kg and above) produced changes in cortical levels of norepinephrine and dopamine, reminiscent of dopamine-beta-hydroxylase inhibition. The results of this series of experiments suggest that somatostatin, in addition to its effects on hormonal regulation, may play an important role in behavior and passive avoidance learning and memory. It is possible that the amnesia produced by cysteamine may have been due to the release of somatostatin into CSF from tissue stores, rather than somatostatin depletion per se. It is also possible that the catecholaminergic effects of high doses of cysteamine contribute to the behavioral deficits observed.