Xylazine is a tranquilizer that is widely used in both biomedical research and veterinary medicine. We now report that in dogs, clinically effective doses of xylazine both markedly decrease basal insulin levels and completely abolish the rise in insulin produced by iv glucose. These changes in insulin levels lead to elevations of fasting plasma glucose and glucose intolerance. In contrast, glucagon levels are unchanged. These studies suggest that xylazine may be a useful agent in the study of glucose metabolism and beta-cell function.