With the availability of a sensitive and specific radioimmunoassay for growth hormone-release-inhibiting hormone (somatostatin or GH-RIH), it was possible to investigate the presence of peptidase enzymes capable of inactivating this hypothalamic hormone in the hypothalamus and other brain areas of the rat. Both supernatant and particulate fractions from male rat hypothalami rapidly inactivated somatostatin, and the enzymes involved have an optimum pH of 7.3. Peptidase activity was significantly higher in the supernatant than in the particulate fraction from the hypothalamus, thalamus, cortex and cerebellum. Besides confirming the presence of peptidases inactivating the release-inhibiting hormone in the hypothalamus (the site of somatostatin synthesis and release) the results may indicate that somatostatin has a functional significance outside the hypothalamus-anterior pituitary axis but within the CNS.