The turnover rate of glucose, the irreversible disposal rate of lactate, and the rate of gluconeogenesis from lactate were calculated by tracer methods in four normal and four alloxan-diabetic dogs under control conditions as well as in chronic, stable metabolic acidosis and alkalosis. Acidosis was produced by feeding dogs 0.8–1 g∙kg−1∙day−1 NH4Clover 1 week, alkalosis was produced by feeding dogs a chloride-free diet and injections of furosemide. Mean plasma pH in the three states were 7.28 ± 0.013, 7.40 ± 0.024, and 7.51 ± 0.015 in normal dogs, and 7.22 ± 0.025,7.42 ± 0.009, and 7.49 ± 0.002 in the diabetic dogs. Respective mean plasma bicarbonate levels were 14.6 ± 0.88, 22.0 ± 0.80, and 32.4 ± 1.88 mequiv. in normal dogs, and 12.3 ± 1.30, 22.6 ± 0.66, and 35.0 ± 1.14 mequiv. in diabetic animals. In normal dogs shifts in acid–base balance had no effect on the level of plasma glucose or the turnover rate of glucose. In diabetic dogs plasma glucose level was significantly elevated by alkalosis. Plasma lactate was positively correlated with plasma pH(r = 0.69, p < 0.01) and was in general higher in diabetic than in normal animals. The increment in concentration was due to a decreased clearance of lactate from the plasma. The irreversible disposal rate was not changed by the acid–base status. Whereas a larger fraction of lactate removed from the plasma appeared in glucose in diabetic animals, this fraction was not changed significantly by shifts in the acid–base status. The glycemic response to i.v. injected 0.05 U/kg insulin was not appreciably altered by the shifts in acid–base status in either normal or diabetic dogs. Stable metabolic acidosis and alkalosis of moderate degree has little effect on glucose and lactate kinetics and gluconeogenesis from lactate in either normal or diabetic dogs.