In Part 1, amphotericin B-induced synovitis of the left tarsocrural joint was used to create hindlimb lameness in 11 horses. Caudal epidural catheters were placed and advanced to the lumbosacral region. Baseline heart and respiratory rates were recorded and horses were videotaped at a walk and trot. Treated horses received 0.2 mg/kg morphine sulfate and 30 ug/kg detomidine hydrochloride through the epidural catheter; control horses received an equivalent volume of physiologic saline solution through the catheter. At hourly intervals after epidural injection for a total of 6 hours, heart and respiratory rates were recorded and horses were videotaped walking and trotting. At the end of the observation period, video recordings were scrambled onto a master videotape. Lamenesses were scored by 3 investigators. Lameness grades, heart rates and respiratory rates were compared. There was a significant decrease in lameness grades after treatment with epidural morphine and detomidine. Initially, heart rates significantly increased in control horses and decreased in treated horses. A similar trend occurred for respiratory rates. In Part 2, caudal epidural catheters were used to administer injections to 10 horses every 12 hours for 14 days. Treated horses received 0.2 nlg/kg morphine sulfate and 30 ug/kg detomidine hydrochloride, and control horses received an equivalent volume of physiologic saline solution. Body weights were recorded on days 1 and 14. Rectal temperature, heart rate, respiratory rate and gastrointestinal motility were recorded twice daily, and daily hay and water consumption was measured. Horses were euthanatized day 15. Atlanto-occipital cerebrospinal fluid samples were submitted for bacteriologic culture and determination of white and red blood cell counts and protein and glucose concentrations. Post mortem examinations were performed and representative samples of the spinal cord and surrounding tissues were taken from cervicothoracic, thoracolumbar, lumbosacral, sacral and catheter entry point regions. Spinal tissue segments from these regions were graded for histologic degree of inflammation and fibrosis. Cerebrospinal fluid values and spinal tissue segment inflammation and fibrosis grades were compared between control and treated horses, and between all 10 catheterized study horses and 6 uncatheterized horses. No problems were encountered with epidural catheter maintenance or injection. No significant difference was identified in body weight change, daily variables or hay and water consumption between control and treated horses. All cerebrospinal fluid cultures were negative for growth. No significant difference in cerebrospinal fluid values or spinal tissue inflammation or fibrosis grades for any segment was demonstrated between control and treated horses. However, when compared to uncatheterized horses, cerebrospinal fluid red blood cell counts were marginally higher and protein concentrations were significantly higher in catheterized horses. As well, lumbosacral and sacral spinal tissue segment inflammation grades and sacral segment fibrosis grades were significantly higher in catheterized compared to uncatheterized horses. Results of these studies indicate that an epidural combination of morphine and detomidine provides profound hindlimb analgesia in horses and is not associated with apparent adverse systemic effects. Localized epidural inflammation and fibrosis appear to be catheter-related. / Master of Science