Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1-4 days with morphine (5, 10, 20 or 30 mg/kg, i.p.) or saline and then received ibogaine (40 mg/kg, i.p.) 5 h after the last morphine pretreatment dose. Compared to rats pretreated with saline, rats pretreated with morphine (10, 20 or 30 mg/kg, i.p.) before ibogaine (40 mg/kg, i.p.) showed a significant reduction in morphine-induced (5 mg/kg, i.p.) locomotor stimulation when tested 29 h after ibogaine administration. Furthermore, this effect was apparent over a range of ibogaine (5-60 mg/kg, i.p.) and morphine test (2.5-5 mg/kg, i.p.) dosages. Doses of ibogaine (5 and 10 mg/kg, i.p.) which alone were inactive inhibited morphine-induced locomotor activity when rats had been pretreated with morphine. These results, showing that morphine pre-exposure affects ibogaine activity, suggest that variable histories of opioid exposure might account for individual differences in the efficacy of ibogaine to inhibit opioid addiction.