The effects of serotonergic manipulations on tonic immobility (TI) were examined. Systemic injections of tryptophan enhanced TI duration. This effect was reversed by quipazine, a 5-HT receptor agonist, and p-chloroamphetamine, a 5-HT releaser. Separately, these drugs caused marked reductions in TI duration. Fenfluramine, which promotes 5-HT release, also reduced TI duration. The quipazine attenuation of TI was prevented by pretreatment with the 5-HT receptor blocker cinanserin. The results are discussed in terms of 5-HT receptor mechanisms and the raphe model of tonic immobility.