The alcohol-preferring AA rats have previously been shown to drink more solution containing the opioid etonitazene than the alcohol-avoiding ANA rats. The present experiments were initiated to see whether the line difference in opioid and alcohol intake would persist if an intravenous (i.v.) route of self-administration is used. Following establishment of stable heroin responding (0.03 mg/kg per infusion), AA and ANA rats were first subjected to three within-session dose-response determinations during which they were allowed to respond for ascending heroin doses (0.0075, 0.015, 0.03, and 0.06 mg/kg per infusion) and then to one progressive-ratio schedule session. AA rats obtained more heroin infusions than ANAs during the first acquisition sessions but there were no significant differences between the lines either in their baseline heroin responding, across the ascending within-session doses, or on the progressive ratio probe. When, after additional heroin baseline sessions, ethanol (1.0 mg/kg per infusion) was substituted for heroin, AA rats initially increased their responding and showed stable rates for responding across ascending ethanol doses (2.0 and 4.0 mg/kg), whereas ANAs declined below their heroin baseline. These findings give evidence for only an initial line difference in i.v. opiate self-administration but for a sustained difference in i.v. ethanol self-administration, thus suggesting that the differential alcohol drinking of the AA and ANA rats is dependent at least partly on non-oral factors.