The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and the untrained muscle in healthy adult young males, both at baseline as well as in response to an acute bout of exercise. Overall design: We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimen of endurance-trained athletes (ET; n = 8; age, 25.4 ±3.8; VO2max, 67.2 ±8.9 ml/min/kg) and sedentary untrained volunteers (SED; n = 8; age, 22.6 ±2.8; VO2max, 40.3 ±7.6 ml/min/kg) using Human Genome U219 (HG-U219) microarray platform. The acute exercise protocol that consisted of 60 min of high intensity cycling exercise on a cycle ergometer at a power requiring 80% of the individual VO2max (including 10 min of initial warm-up cycling at 60% VO2max). Baseline samples of the resting muscle were obtained 24 hours before the acute exercise protocol was started. Post exercise biopsies were taken at 30 min (+30') and at 3 hours (+3 h) after cessation of acute cycling exercise.