The metabolic effects of partial ischemia on canine skeletal muscle were examined during 20 min of isometric contraction. A reduction in blood flow of approximately 75% resulted in an approximate 40% reduction in contractile function. Muscle lactate accumulation and phosphocreatine (PCr) hydrolysis were greater during ischemia, indicating a greater reliance on anaerobic ATP regeneration. Pyruvate dehydrogenase transformation to its active form (PDCa) during contraction was not affected by ischemia, such that PDCa did not appear to be a determinant of skeletal muscle fatigue. Acetylcarnitine concentration was greater during ischemic contraction and inversely correlated with PCr concentration (r = -0.79, P<0.01). Furthermore, acetylcarnitine accumulation and PCr degradation correlated with the degree of skeletal muscle fatigue (r = 0.56, P<0.05 and r = 0.70, P<0.01, respectively). Thus the greater the acetyl group oxidation, the lesser the contribution from anaerobic ATP provision and, subsequently, the smaller the degree of muscle fatigue observed. The metabolic characteristics of this model of ischemic muscle contraction are indistinguishable from the normal metabolic responses observed with increasing contractile intensity.