The reinforcing effects of intravenously delivered cocaine, alfentanil, morphine, heroin, nalbuphine, or buprenorphine were evaluated in four rhesus monkeys before, during, and after daily administration of 3.2 mg/kg morphine. Morphine was given 21 h prior to measures of the reinforcing effects of each of the drugs. No changes in the potency of cocaine or the high efficacy mu agonist alfentanil were detectable during the period of chronic morphine administration. Small (1/2-1) log unit decreases in the reinforcing potency of intermediate efficacy mu agonists morphine and heroin occurred during chronic morphine administration. Larger decreases in both the potency and effectiveness of low-efficacy mu agonists nalbuphine and buprenorphine developed during this time. These data suggest that the amount of tolerance that develops to the reinforcing effects of opioids depends on the efficacy of the drugs used to maintain responding.