The purpose of this study was to assess noninvasively both the "oxidative potential" and the sequence of metabolic events that occur during the transition from rest to fatigue in an isometrically exercising muscle. 31P-magnetic resonance spectroscopy was used to obtain continuous measures of intracellular phosphocreatine (PCr), inorganic phosphate (Pi), and proton concentration ([H+]) in the tibialis anterior muscle of eight healthy human volunteers during a progressive isometric exercise protocol. The exercise protocol consisted of 2-min stages, with a duty cycle consisting of 4 s of contraction and 6 s of relaxation, beginning at 10% of the force from an initial maximal voluntary contraction (MVC) and increasing by 10% to a final load of 80% MVC. An MVC was performed at the beginning of each stage; a decrease in MVC indicated fatigue. The initial linear slope of the relationship between force and Pi/PCr was used as an index of oxidative potential for the muscle. This initial slope ranged from 85 to 167% MVC/(Pi/PCr), indicating substantial variability of oxidative potential in these subjects. The changes in Pi/PCr and [H+] over time were best described with a bilinear fit of the individual data. The inflection point for each fit was defined as the point at which the slopes intersected. The Pi/PCr inflection point occurred at a similar value of Pi/PCr in all subjects [0.47 +/- 0.04 (SE)]. The Pi/PCr inflection point occurred significantly earlier (7.8 +/- 0.7 min) than the [H+] inflection point (9.3 +/- 0.4 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)