L-Tryptophan (100 mg/kg, IP), the serotonin [5-hydroxytryptamine (5-HT)] amino acid precursor, significantly reduced the mean breaking point maintained under a self-administration progressive ratio schedule of IV cocaine reinforcement (0.6 mg/injection). This effect was produced over the 5 days of self-administration following treatment. Responding maintained under the same progressive ratio schedule for food reinforcement was not affected by L-tryptophan (100 mg/kg, IP). Rats administered L-tryptophan (100 mg/kg, IP) and denied access to cocaine on the day of treatment resumed normal self-administration patterns under a progressive ratio schedule on following test days. This indicates that L-tryptophan treatment alone did not induce long-term effects on cocaine self-administration. Thus, it would appear that the combination of this 5-HT manipulation and cocaine administration altered the reinforcing efficacy of the drug and induced a long-term decrement in breaking point under a progressive ratio schedule. This may have been due to an associative aversion to cocaine self-administration behaviour learned on the day of treatment and carried over to the subsequent 5 days of self-administration access.