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Abstract: Microdialysis is a valuable tool to measure tissue responses. We hypothesized that skeletal muscle metabolism can be modulated by microdialysis applied drugs which alter cytosolic calcium concentration. With approval of the local animal care committee, the hind limbs of sacrificed male Sprague Dawley rats were perfused either with Ringer's solution or with dantrolene 1 μM at 30 ml hr−1 and 21 °. Microdialysis probes in both hind limbs were perfused at 1 μl min−1 either with sorbitol 80 mM, calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% respectively, and at the contralateral adductor muscle with Ringer as control. Lactate was measured spectrophotometrically in the dialysate at 15 min. intervals. Lactate levels as measured by intramuscular microdialysis were not influenced by intramuscular application of sorbitol 80 mM compared to control measurements with Ringer's solution. Local application of calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80 mM, and halothane 10 vol% via microdialysis increased lactate concentrations, while organ perfusion by dantrolene 1 μM reduced the caffeine-induced lactate increase. Modulation of intramuscular lactate metabolism by exogenous compounds via microdialysis probes generates new insights in skeletal muscle metabolism.