Rats were implanted with microdialysis probes in hippocampi and striata, and somatostatin-like immunoreactivity (SS-LI) was measured in outflows obtained from awake, freely moving animals 48 and 72 h post implantation. SS-LI was measurable in all dialysates under basal conditions; concentrations were stable and within a narrow range, about 3-6 fmol/ml. Cysteamine (300 mg/kg, s.c.) markedly reduced basal SS-LI concentrations in outflows from hippocampus (P < 0.00001). KCl (100 mM, 10 min) or veratridine (50 microM, 10 min) infusion elevated hippocampal SS-LI output by 55 and 106%, respectively (P's < 0.05). EGTA (10 mM) or tetrodotoxin (2 microM) infusion inhibited the SS-LI release elicited by KCl and veratridine, respectively, without affecting the basal SS-LI outflow. Thus, our results demonstrate that SS-LI is released from rat hippocampus and striatum in vivo, and provide evidence that the peptide may be released in hippocampus by both action potential dependent and independent processes.