The technique of microdialysis was employed to investigate in vivo 5-hydroxytryptamine (5-HT) release in isolation-reared rats compared with socially reared rats. Two methods were employed to stimulate 5-HT release: local KCl injection into the frontal cortex of chloral hydrate anaesthetized rats, and the exposure of freely moving rats to a novel environment (the elevated x-maze). Microdialysis probes were implanted into the frontal cortex in the case of KCl stimulation and the ventral hippocampus in the case of exposure to the novel environment, and perfused with artificial CSF (1 μl/min). Dialysis samples were collected every 20 min and analysed for 5-HT and 5-hydroxyindole acetic acid (5-HIAA) by HPLC with electrochemical detection. Both KCl injection (1 μl, 100 mM) and a 20 min period on the elevated x-maze produced a significant increase in extracellular 5-HT in the socially reared rats. Neither the increase in extracellular 5-HT induced by KCl nor the increase on exposure to the elevated x-maze were observed in the isolation-reared rats. Dialysate 5-HIAA was not affected in socially reared or isolation-reared rats, in either protocol. These results suggest that isolation-reared rats have a reduced presynaptic neuronal function to release 5-HT.