The study demonstrates that guinea-pigs handled daily from birth exhibit similar behaviour to rats on the elevated plus maze. Simultaneously performed intra-cortical microdialysis showed that placing guinea-pigs on the elevated plus maze results in an increase in extracellular 5-HT in the frontal cortex. 8-OH-DPAT (0.3 mg/kg s.c.) reduced significantly the increase in cortical extracellular 5-HT and resulted in an 'anxiolytic' profile of behaviour. Pre-treatment with the 5-HT(1) antagonist methiothepin (10.0 mg/kg) antagonized the behavioural effects and prevented the increase in cortical extracellular 5-HT normally produced by exposure to the elevated plus maze. Methiothepin alone had no effect on behaviour in the elevated plus maze. 5-CT (0.1 mg/kg i.p.) abolished the rise in extracellular 5-HT, but did not produce an 'anxiolytic' profile of behaviour on the elevated plus maze. The results show that an increase in cortical extracellular 5-HT occurs in the saline- treated guinea-pig exposed to aversive conditions. It remains to be determined whether the 'anxiolytic' effect of 8-OH-DPAT in the guinea-pig is causally associated with decreased basal extracellular 5-HT. The results however indicate that there is no simple relationship between inhibition of 5-HT release and behaviour indicative of 'anxiolytic' drug actions.