The effects of three serotonin [5-hydroxytryptamine (5-HT)] receptor antagonists on cocaine self-administration behavior were investigated. Specifically, the effects of MDL 72222 (a specific 5-HT3 receptor antagonist), ketanserin (a specific 5HT2 receptor antagonist), and methysergide (an aselective 5-HT1/5-HT2 receptor antagonist) on the breaking points reached by rats on a progressive ratio schedule for cocaine reinforcement were examined. Pretreatments with MDL 72222 (7.5-1,920 micrograms/kg, SC), ketanserin (0.4-6.4 mg/kg, IP), and methysergide (2.5-20 mg/kg, IP) failed to alter breaking points from baseline values. Although tested at twice the highest doses previously reported to have significant behavioral effects, the three 5-HT receptor antagonists were without effect. These data suggest that relatively specific blockade of 5-HT receptor subtypes does not influence the reinforcing effects of cocaine.