The release of [3H]5-HT from guinea-pig frontal cortex slices was elicited by continuous exposure to Krebs solution containing elevated K+ ions (30 mM) and 10 microM fluvoxamine. K+-stimulated release was inhibited by 5-carboxamidotryptamine (pIC25 8.1), 5-HT (7.4), RU 24969 (6.5) and GR 43175 (6.4). 8-OH-DPAT was without effect on K+-evoked release of [3H]5-HT at concentrations up to 1 microM. The inhibitory effects of 5-HT were antagonised by metitepine (pA2 8.2), metergoline (7.0), methysergide (6.5), cyanopindolol (6.5), yohimbine (6.5) and mesulergine (6.2) but not by the 5-HT3 antagonist, ICS 205-930 (1 microM). The results are discussed in the context of the known pharmacology of 5-HT receptor subtypes. It is concluded that the 5-HT receptor modulating 5-HT release in the guinea-pig frontal cortex does not correspond to any of the 5-HT1-subtype recognition sites or to 5-HT2 or 5-HT3 receptors.