In isolated, blood perfused, supramaximally stimulated, isotonically working gastrocnemii of dogs lactic acid (LA) output and O2-consumption (V O2) were measured according to the Fick principle. Simultaneously concentration of muscle tissue was determined at rest and at different times during exercise. In one series of experiments metabolic alkalosis was induced by infusions of THAM of Na bicarbonate. As a result arterial pH increased to about 7.5 and standard [HCO3-1] to 31-35 mmol per 1. In another group of experiments metabolic acidosis was induced by HCl infusions. In these experiments pH decreased to 7.0-7.1 and standard [HO301] to 8-11 mmol per 1. During the first 3-4 min after the onset of exercise LA concentration of muscle tissue rose to 18-19 mumol per g wet weight in both series of experiments. During acidosis the highest average values for LA release from the muscle were about 1.1 mumoles per g per minute. During alkalosis LA permeation rate was nearly three times as high. As a consequence of increased rate of permeation, LA concentration of muscle tissue decreased more rapidly in alkalosis than in acidosis. In both series of experiments work per time and VO2 were practically equal during the first 5-6 min of exercise. Thereafter work per time and VO2 decreased more rapidly in acidosis than in alkalosis, a result which probably is due to higher LA concentration in muscle at this time in acidosis. It is concluded that LA permeation rate across muscle cell membrane is increased by high extracellular HCO3- concentration in combination with low H+ activity and vice versa.