To examine whether blood lactate and ammonia concentrations can be used to estimate the functional state of the muscle contractile machinery with regard to muscle lactate and adenosine triphosphate (ATP) levels during leg press exercise. Thirteen men (age, 34 ± 5 years; 1 repetition maximum leg press strength 199 ± 33 kg) performed either 5 sets of 10 repetitions to failure (5×10RF), or 10 sets of 5 repetitions not to failure (10×5RNF) with the same initial load (10RM) and interset rests (2 minutes) on 2 separate sessions in random order. Capillary blood samples were obtained before and during exercise and recovery. Six subjects underwent vastus lateralis muscle biopsies at rest, before the first set and after the final exercise set. The 5×10RF resulted in a significant and marked decrease in power output (37%), muscle ATP content (24%), and high levels of muscle lactate (25.0 ± 8.1 mmol·kg wet weight), blood lactate (10.3 ± 2.6 mmol·L), and blood ammonia (91.6 ± 40.5 μmol·L). During 10×5RNF no or minimal changes were observed. Significant correlations were found between: (a) blood ammonia and muscle ATP (r = -0.75), (b) changes in peak power output and blood ammonia (r = -0.87) and blood lactate (r = -0.84), and (c) blood and muscle lactate (r = 0.90). Blood lactate and ammonia concentrations can be used as extracellular markers for muscle lactate and ATP contents, respectively. The decline in mechanical power output can be used to indirectly estimate blood ammonia and lactate during leg press exercise.