The purpose of the present experiment was to determine whether the effects of opioids with varying degrees of efficacy at the mu receptor are differentially altered in morphine-tolerant pigeons. To this end, dose-effect curves were determined for high, intermediate, and low efficacy mu agonists in pigeons responding under a schedule of food presentation prior to, during, and after exposure to a regimen of chronic morphine administration. In pigeons treated with 56 mg/kg/daily morphine, the dose-effect curves for the rate-decreasing effects of the high-efficacy mu agonists morphine and fentanyl were shifted to the right of their prechronic positions (i.e., tolerance). A small degree of tolerance was also conferred to the intermediate-efficacy mu agonists (-)-pentazocine and (-)-metazocine, but not to nalbuphine or butorphanol. In contrast to the effects obtained with these mu agonists, the chronic morphine regimen shifted the dose-effects curves of the mu antagonist naloxone and the low-efficacy mu agonists nalorphine and levallorphan to the left of their prechronic positions (i.e., enhanced sensitivity). These findings demonstrate that morphine tolerance confers cross-tolerance to other high efficacy mu agonists, enhanced sensitivity to mu antagonists and low efficacy mu agonists, and little or no cross-tolerance to intermediate efficacy mu agonists. Disadvantages of using schedule-controlled responding to examine the effects of intermediate efficacy mu agonists are discussed.