Extracellular levels of somatostatin in the rat striatum were studied using in vivo microdialysis and radioimmunoassay. In vitro studies were performed using three different dialysis membranes at various flow rates and temperatures to assess the optimal recovery of somatostatin. The best results were obtained when a cellulose fibre membrane was utilized at 37 degrees C with a flow rate of 0.5 microliters/min. For the in vivo studies, transcerebral cellulose probes were implanted in the striatum of chloryl hydrate-anaesthetized rats. Basal levels of somatostatin were detected in the striatum of the freely moving animals and found to be 5-15 fmol. Stimulation with 100 mM KCl increased the recovered somatostatin by 138% (P < 0.05). A second stimulation following a 3-h interval increased the somatostatin levels by approximately 60%. The addition of veratridine (100 microM) in the perfusion medium increased the somatostatin levels recovered from the striatum by 85% (P < 0.01). Following a 3-h interval, a second stimulation by veratridine also increased somatostatin levels (43%). The increases observed after the second depolarizing stimulus (KCl and veratridine) were not found to be significantly different from basal levels. Both EGTA and the sodium channel blocker tetrodotoxin attenuated the effect of KCl and veratridine, respectively. However, neither EGTA nor tetrodotoxin had an effect on the basal levels of somatostatin recovered. These results indicate that (i) the somatostatin measured is neuronally released in the striatum and (ii) microdialysis is a useful tool for examining the regulation of somatostatin release in the brain.