The effects of somatostatin (SS-14) (0.1-10 micrograms, i.c.v.) on brain histamine (HA) in male Wistar rats were investigated. HA was measured by HPLC with a cation exchanger and an automated fluorometric detection system. SS-14 induced time- and dose-dependent changes in the levels of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, hippocampus, and frontal cortex. In the anterior hypothalamus, posterior hypothalamus and hippocampus, SS-14 (1 microgram, i.c.v.) significantly (p less than 0.01) decreased the levels of HA from 5 to 30 min. This response was delayed by 5 min in the frontal cortex and adenohypophysis. Only in the neurohypophysis, SS-14 increased the concentration of HA 10 min after injection, but this response was not dose-related. These results seem to indicate that SS-14 influences neuronal HA probably modifying HA release, it leading to a decrease of the levels of the biogenic amine in specific areas of the brain. Since this effect is opposite to that developed by growth hormone-releasing factor (GRF) in identical conditions, HA seems to fulfil the criteria by which a neuroendocrine modulator should currently respond in a specific time- and dose-dependent manner to those neuropeptides which modulate. Therefore, HA is likely to play a key role as a neuromodulator of the somatotropinergic system in the rat.