Local injection of cysteamine into rat striatum results in a rapid but reversible reduction in somatostatin-like immunoreactivity (SLI). Since somatostatin and neuropeptide Y are co-localized in striatal and cortical neurons, we examined the effects of cysteamine in these areas. SLI and neuropeptide Y-like immunoreactivity (NPYLI) were measured following local injection of cysteamine into the striatum. In addition, we examined the effects of cysteamine on SLI and NPYLI in cortical synaptosomes. SLI was significantly reduced in both experiments, but NPYLI was unaffected. These results suggest that the mechanism by which somatostatin is depleted by cysteamine is one of specific biochemical modification, probably affecting the somatostatin disulfide bond, rather than one affecting neuronal metabolism.