The 5-hydroxytryptamine (5-HT, serotonin) specific presynaptic reuptake inhibitor Lilly 110140 (fluoxetine hydrochloride) was injected systemically in rats trained to bar-press for rewarding stimulation to the caudal portion ofthe medial forebrain bundle. Rates of self stimulation were reduced in proportion to drug dosage, and these reductions were partially reversible by methysergide. These findings are consistent with previous reports suggesting an inhibitory role for 5-HT in self stimulation.