Ligand binding studies identified certain serotonin (5-HT) antagonists with selective affinity for 5-HT2 receptors and other serotonin antagonists with affinity for both 5-HT1 and 5-HT2 receptors. The actions of ketanserin and pipamperone, selective 5-HT2 receptor antagonists were compared with metergoline and methysergide, nonselective 5-HT antagonists, on 2 behavioral responses in rats that are produced by the activation of 5-HT receptors, i.e., the head shake response and the 5-HT syndrome. Both the selective and the nonselective 5-HT antagonists blocked the head shake response produced by 5-hydroxy-L-Trp. The order of relative potency was metergoline > ketanserin > pipamperone > methysergide. All 4 antagonists also blocked the head shake response produced by the 5-HT agonist quipazine. The symptoms of the 5-HT syndrome produced by 5-methoxy-N,N-dimethyltryptamine were blocked by pretreatment with the nonselective 5-HT receptor antagonists but not by the 5-HT2 receptor antagonists. The differential actions of 5-HT antagonists on these behavioral responses suggest that different 5-HT receptors are involved in the head shake response and the 5-HT syndrome. That the order of relative potency for these drugs to block the head shake response was the same as their reported affinity for the 5-HT2 receptor suggests that the 5-HT2 receptor is involved in the head shake response. The ability of 5-HT antagonists with affinity for the 5-HT1 receptor to block the 5-HT syndrome and the inability of 5-HT2 receptor antagonists to block the syndrome suggests that this behavioral response involves the activation of 5-HT1 receptors.