Male Sprague-Dawley rats deprived of food for 18 h were injected with the 5-HT agonists RU 24969, 1-(3-chlorophenyl)piperazine (mCPP) or 1-[3-(trifluoromethyl)phenyl)]piperazine (TFMPP) and 20 min later presented with their normal diet. Food intake was determined 1, 2 and 4 h later. All three drugs reduced intake over 1 and 2 h. Three out of four drugs with high affinity for 5-HT1C receptors (metergoline, mianserin, and mesulergine but not cyproheptadine) opposed hypophagia caused by mCPP. Another drug reported to have high affinity for the 5-HT1C site, 1-naphthyl-piperazine (1-NP), also blocked the hypophagic response to mCPP at doses which attenuated mCPP-induced hypolocomotion. Only one of the above drugs (metergoline) which also has high affinity for other 5-HT sites opposed hypophagia caused by RU 24969. Two out of three 5-HT1B receptor antagonists [(+/-) cyanopindolol, (-) propranolol, but not (-) pindolol)] which oppose hypophagia caused by RU 24969 (Kennett et al. 1987) also opposed hypophagia caused by mCPP. The 5-HT2 antagonists ketanserin and ritanserin, the 5-HT3 antagonist ICS 205-930 and the alpha 2 adrenoceptor antagonist idazoxan did not oppose the hypophagic effect of mCPP. In agreement with results for mCPP, hypophagia caused by TFMPP was opposed by both, mianserin and (+/-) cyanopindolol. Given alone, mianserin 1-NP and cyproheptadine but not ICS 205-930 increased food consumption of normally fed rats. The results suggest that RU 24969-induced hypophagia depends on 5-HT1B receptors but not on 5-HT1C receptors, while mCPP (and TFMPP)-induced hypophagia may depend on both receptors.(ABSTRACT TRUNCATED AT 250 WORDS)