These studies demonstrated the acquisition and extinction of conditioned tolerance to the analgesic effect of nicotine in rats. In Experiment 1, distinctive environmental cues were either paired or unpaired with nicotine. Following acquisition, the paired group was more tolerant to nicotine than the paired with nicotine. Following acquisition, the paired group was more tolerant to nicotine than the unpaired and saline groups. Conditioned tolerance was extinguished in the paired group after placebo sessions in the distinctive environment. Experiment 2 examined whether the distinctive environment functioned as a CS or as an occasion setter for injection cues. After acquisition, exposure to the distinctive environment, with or without placebo injections, resulted in extinction. This demonstrates that the distinctive environment served as a CS, not as an occasion setter for injection cues.