OBJECTIVE To assess effects of buprenorphine hydrochloride (BH), sustained-release buprenorphine (SRB), and high-concentration buprenorphine (HCB) formulations in healthy rats. ANIMALS 8 Sprague-Dawley rats. PROCEDURES In a crossover-design study, rats received BH (0.05 mg/kg), SRB (1.2 mg/kg), HCB (0.30 mg/kg), or 5% dextrose solution (0.2 mL/kg), SC, once. Self-injurious behavior and thermal sensitivity (hind limb withdrawal latencies) were assessed prior to injection (time 0) and 1, 4, 8, 12, and 24 hours after injection. Food intake, kaolin intake, and fecal output were measured over 12-hour light and dark periods before and after each treatment. Values were compared among treatments and time points. RESULTS Self-injurious behavior was detected with all buprenorphine treatments; scores were greater at all time points during the 12 hours after HCB and 24 hours after SRB administration than at time 0. Percentage change in hind limb withdrawal latencies from time 0 was higher with BH and HCB 1 hour after injection than at other time points. Postinjection light-period food intake was higher (BH and HCB) and dark-period food intake was lower (BH, HCB, and SRB), compared with preinjection values for the same treatments. For SRB, postinjection light-period kaolin intake was greater than the preinjection value, and postinjection light- and dark-period kaolin intake was greater than that for other treatments. CONCLUSIONS AND CLINICAL RELEVANCE Hypoalgesic effects were briefly observed after administration of BH or HCB in healthy rats; adverse effects were detected in some rats with all buprenorphine formulations. Studies comparing effects of BH, SRB, and HCB in rats undergoing surgery or other noxious stimuli are indicated to determine clinical benefits in this species.