Determined if variations in opioid pretreatment time would affect how muopioid agonists interact with cocaine. Rats were trained to discriminate 10 mg/kg cocaine from saline. One group of Ss received morphine prior to cumulative doses of cocaine. These pretreatment times were selected to overlap with states of acute opioid tolerance or acute opioid dependence as demonstrated by previous studies. A 2nd group was administered naloxone 5 min prior to cumulative cocaine doses, with or without a 4-h morphine or methadone pretreatment. In a 3rd procedure, the same Ss used in the 2nd experiment were also tested for time-dependent changes in the analgesic effect of morphine using a hot-plate assay. Morphine pretreatment 1 h prior to assessment of the cocaine dose-response function significantly enhanced the discriminative stimulus effects of cocaine. However, neither 0.5-h or 4-h morphine pretreatment had any effect. When naloxone was administered 4 h following either morphine or methadone and 5 min prior to assessment of the cocaine dose-response curve, the discriminative stimulus effects of cocaine were significantly attenuated. In assessing morphine-induced analgesia, paw-lick latency was significantly longer at 1 h and shorter at 4 h following morphine administration.