This study examined the effects of extracellular alkalosis on the metabolism and performance of perfused rat hindlimb muscles during electrical stimulation. Three acid-base conditions were used: control (C, normal acid-base state), metabolic alkalosis (MALK, increased bicarbonate concentration), and respiratory alkalosis (RALK, decreased PCO2). A one-pass system was used to perfuse the hindlimb via the femoral artery for 20 min at rest and during 5 min of tetanic stimulation via the sciatic nerve. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded. Arterial and venous perfusates were periodically sampled for substrate and metabolite measurements, and muscle samples were taken pre- and postperfusion. Peak isometric tensions in C, MALK, and RALK were similar: 3,367 +/- 107, 3,317 +/- 110, and 3,404 +/- 69 g, respectively. The rate of tension decay was also unaffected by alkalosis and represented 78 and 55% of the peak tension following 2 and 5 min of stimulation, respectively. Muscle O2 uptake, glycogen utilization, and total lactate (La-) production were similar following 5 min of stimulation in all conditions. However, alkalosis resulted in an enhanced La- release from working muscle (peak La- release: C, 15.5 +/- 1.1; MALK, 19.7 +/- 1.6; RALK, 18.3 +/- 2.2 mumol/min), and a 15-20% reduction in intramuscular La- accumulation. Alkalosis had no effect on muscle creatine phosphate and ATP concentrations. Thus, in the perfused rat hindlimb, alkalosis was not associated with changes in tetanic force or glycolysis, but La- release from the working muscle was enhanced by increased extracellular pH and bicarbonate.