Rationale: The combined administration of heroin and cocaine ('speedball') is common among intravenous drug users. Dopamine receptors in the nucleus accumbens play a key role in cocaine self-administration; however, their role in speedball self-administration is unknown, as is the role of opiate receptors in this region. Objectives: The effect of blocking dopamine D1, D2, μ-opiate or δ-opiate receptors in the nucleus accumbens on the intravenous self-administration of combined heroin and cocaine was examined in rats. Methods: Rats with bilateral cannulae implanted into the nucleus accumbens were trained to self-administer intravenous speedball (ratio of cocaine/heroin, 17:1) under a progressive ratio (PR) schedule. Prior to their self-administration session, rats were then microinjected with the dopamine D1 receptor antagonist SCH 23390 (1 and 6 nmol side-1), the D2 receptor antagonist raclopride (3 and 10 nmol side-1), the μ-opiate receptor antagonist CTOP (0.1, 0.3 and 1.0 nmol side-1), the δ-opiate receptor antagonist naltrindole (1.0, 3.0 and 10 nmol side-1) or a cocktail of SCH 23390 (1 nmol side-1) and CTOP (0.1 nmol side -1) into the nucleus accumbens. Results: Microinjection of SCH 23390, raclopride or CTOP into the nucleus accumbens produced dose-dependent decreases in breakpoints under the PR schedule, while naltrindole was without effect. The highest dose of SCH 23390 also significantly reduced locomotor activity measured during speedball self-administration. The combination of SCH 23390 and CTOP significantly reduced breakpoints, while not affecting locomotor activity. Conclusions: These results indicate that dopamine and μ-opiate receptors, but not δ-opiate receptors, in the nucleus accumbens are involved in the reinforcing effects of speedball. Combined administration of D1 and μ-opiate receptor antagonists may be more selective at reducing the reinforcing effects of speedball self-administration than either drug alone.