Injection of d-amphetamine into the nucleus accumbens potentiates responding for stimuli paired with a primary reward. A previous study showed that this potentiating effect of d-amphetamine on responding for conditioned reward (CR) was attenuated by peripherally injected d-fenfluramine, a 5-hydroxytryptamine (5-HT) releaser and re-uptake inhibitor. The present experiments further examined the effects of manipulating 5-HT function within the nucleus accumbens on responding for CR, and on the potentiation of CR responding following intra-accumbens injection of d-amphetamine. Water deprived rats were trained to associate a compound stimulus with water delivery during a conditioning phase. During a test phase water was not delivered, but the compound stimulus was delivered according to a random ratio 2 schedule following a response on one of two levers. Rats responded at a higher rate on the lever delivering this CR. d-Amphetamine (10 micrograms) injected into the nucleus accumbens enhanced responding on the CR lever. Co-injections of 5-HT (5 and 10 micrograms) into the nucleus accumbens abolished the response-potentiating effect of d-amphetamine but were without effect on the base-line level of responding for CR. This reduction by 5-HT of the response potentiating effect of d-amphetamine was prevented by prior treatment with the 5-HT receptor antagonist metergoline (1 mg/kg). Responding for water was not altered by 5-HT and so the effects of 5-HT on responding for CR cannot be due to a change in the motivation to seek the primary reward. Thus, elevating 5-HT activity within the nucleus accumbens antagonises the effect of d-amphetamine on responding for CR within the nucleus accumbens. These results suggest that 5-HT within the nucleus accumbens may play an important role in mediating incentive motivation by modulating dopaminergic neurotransmission.