Two series of experiments examined whether 5-hydroxytryptamine (5-HT) antagonists induce feeding in rats. In the first series of experiments separate groups of rats were injected with various doses of methysergide, cyproheptadine, metergoline or ritanserin prior to a 2 h period of access to a wet mash diet which induced vigorous feeding under control conditions. None of the antagonists increased food intake in this paradigm. Rather, at certain doses, methysergide, cyproheptadine and ritanserin induced slight decreases in food intake. Since 5-HT may be involved in controlling satiety, it may be that a more appropriate test of the efficacy of these compounds involves administering them to maximally satiated rats. Consequently, the effects of these drugs were investigated in groups of rats which had fed to satiety immediately prior to drug treatment. In this paradigm methysergide, metergoline and ritanserin, but not cyproheptadine, induced definite increases in food intake. It is suggested that this effect occurs via a dissipation of satiety signals, and that these results further support the hypothesis that 5-HT is involved in controlling satiety. The possibility that these antagonists act on peripheral 5-HT systems is discussed.