This study assessed the blockade of hydromorphone challenge effects (cumulative s.c. doses of 0, 6 and 18 mg) during chronic buprenorphine treatment of opioid dependent subjects. Buprenorphine was administered daily via the sublingual route in ascending doses of 2, 4, 8 and 16 mg. Hydromorphone challenges were conducted after 10 to 14 days of chronic administration of each buprenorphine dose and 24 h after the last buprenorphrine dose. Buprenorphrine itself only produced dose-related effects in respiration rate. While subjects were maintained on 2 mg of buprenorphine, the hydromorphone challenge produced dose-related changes in physiological and self-report measures. As the dose of buprenorphine was increased, hydromorphone effects on self-report measures were attenuated to a greater extent than was noted for pupil diameter. The results of this study confirm previous reports of buprenorphine blockade of opioid agonist effects in humans and extent those findings by demonstrating both a buprenorphine dose-effect function and a dissociation between the potency of buprenorphine's opioid blockade for self-report vs. physiological measures.