The metabolism and performance of a perfused rat hindquarter preparation was examined during heavy exercise in three conditions: control (C), metabolic acidosis (MA, decreased bicarbonate concentration), and respiratory acidosis (RA, increased CO2 tension). A one-pass system was used to perfuse the hindquarters for 30 min at rest and 20 min during tetanic stimulation via the sciatic nerve. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded, and biopsies were taken pre- and postperfusion. Initial isometric tensions were similar in all conditions, but the rate of tension decay was largest in acidosis; the 5-min tensions for C, MA, and RA were 1,835 +/- 63, 1,534 +/- 63, and 1,434 +/- 73 g, respectively. O2 uptake in C was greater than in MA and RA (23.4 +/- 1.3 vs. 17.0 +/- 1.4 and 16.5 +/- 2.3 mumol X min-1), paralleling the tension findings. Hindquarter lactate release was greatest in C, least in MA, and intermediate in RA. Acidosis resulted in less muscle glycogen utilization and lactate accumulation than during control. Muscle creatine phosphate utilization and ATP levels were unaffected by acidosis. Acidosis decreased the muscle's ability to generate isometric tension and depressed both aerobic and anaerobic metabolism. During stimulation in this model lactate left the muscle mainly as a function of the production rate, although a low plasma bicarbonate concentration at pH 7.15 depressed muscle lactate release.