The study was conducted to evaluate the effects of xylazine individually (0.05 mg/kg), ketamine individually (2.5 mg/kg), and a combination of xylazine and ketamine (0.05 mg/kg and 2.5 mg/kg) after lumbar epidural administration in water buffalo calves. Fifteen non-descript, male water buffalo calves of 6-8 months of age weighing between 55 and 75 kg were randomly placed in three groups (groups A, B and C). The agents were administered at the first lumbar epidural space. Clinico-physiological parameters, such as analgesia, ataxia, sedation, salivation, heart rate, respiratory rate and rectal temperature were studied. Other haematological and biochemical parameters monitored were haemoglobin, packed cell volume, total leukocyte count, plasma glucose, cortisol, protein albumin, globulin, blood urea nitrogen (BUN), creatinine, alanineamino transferase (ALT), sodium, potassium and chloride. The onset of analgesia (mean +/- SEM) was faster in group C (3.2 +/- 0.20 min) compared with that of group B (4.6 +/- 0.22 min) and group A (34.0 +/- 1.86 min). Analgesia of the thorax, flank, inguinal region, hind limbs, perineum and tail was complete in group C, but mild to moderate in groups A and B. Ataxia was severe in group C and mild in groups A and B. Mild to deep sedation was produced by groups A and C animals. Group B animals failed to produce sedation. Longer duration and greater depth of analgesia was produced in animals of group C. Heart rate, respiratory rate and rectal temperature decreased in groups A and C. The haematological parameters decreased in all the groups. The biochemical parameters like glucose, cortisol, BUN, creatinine, and ALT increased in all the animals. However, total proteins and albumin decreased in the three groups. The plasma electrolytes sodium, potassium and chloride did not show any significant change. The results of this study indicated a possible synergistic analgesic interaction between epidurally administered xylazine and ketamine, without causing any marked systemic effects in water buffalo calves.