It has been demonstrated that many of the components of the conditional response evidenced in anticipation of morphine are opposite in direction to the effects of the opiate. According to a conditioning model of tolerance, these drug compensatory conditional responses, elicited by predrug environmental cues, attenuate the effect of the drug and thus contribute to tolerance. Experiments supporting this conditioning model of tolerance are summarized. They demonstrate that: the display of tolerance is specific to the environment in which the drug has been previously administered; established tolerance can be extinguished by repeated placebo sessions; interpolating placebo sessions among drug sessions impedes the acquisition of tolerance, i.e., tolerance, like other conditional responses, is hindered by partial reinforcement; and experience with drug administration cues, prior to their pairing with morphine, impedes the acquisition of tolerance, i.e., tolerance, like other conditional responses, is affected by 'latent inhibition'. These data (from Siegel's laboratory), together with findings from other laboratories demonstrating the effects on tolerance of electroconvulsive shock, metabolic inhibitors, and pituitary vasopressin, indicate the importance of associative mechanisms in the acquisition of tolerance.