Significant advances have been made in our ability to assess pain and administer appropriate pain relief in laboratory animals. However, providing long-lasting analgesia using a route that does not involve animal restraint remains difficult. The objective of this study was to investigate whether oral administration of slow-release morphine or hydromorphone results in increased thermal nociception in laboratory rats. The results showed that 64 mg/kg morphine and 16 mg/kg hydromorphone induced comparable increases in foot withdrawal latencies for up to three hours postadministration; however, slow-release morphine increased response latencies for up to 11 hours. Whether these dose rates provide clinically effective pain relief has yet to be determined; however, these data suggest that using slow-release preparations could be an effective and highly practical method of elevating pain thresholds for a relatively prolonged period.