Combination of the 5-HT-uptake inhibitor, citalopram, with 1-5-HTP induced a characteristic head shake syndrome in rats. This was blocked by a range of 5-HT antagonists, including the selective 5-HT2 antagonists, ketanserin and pirenperone and was also blocked by the alpha 1-adrenoceptor antagonists, prazosin and WB 4101, and the alpha 2-adrenoceptor agonist, clonidine. 1-5-HTP-antagonistic effect was also recorded for 26 neuroleptic drugs. Their inhibitory potencies showed close correlation to 5-HT2-receptor affinity in vitro and, slightly weaker, to alpha 1-adrenoceptor affinity. In contrast, no correlation to dopamine D-2 receptor affinity was found, indicating that the cataleptogenic and motility-inhibitory properties of neuroleptics did not unspecifically influence 1-5-HTP-induced head shakes. These were not influenced by a histaminic antagonist, muscarinic antagonist or alpha 2-adrenoceptor antagonist, but were inhibited by beta-adrenoceptor blockers, GABA agonists, a benzodiazepine and morphine. The results indicate that 1-5-HTP-induced head shakes are most sensitive to 5-HT2 antagonists, but that the syndrome is influenced by other neuronal systems. Since 5-HT2 affinity and alpha 1-adrenoceptor affinity of many compounds is found concomitantly, caution is needed to evaluate the relative importance of these properties for 1-5-HTP antagonism.