Low-field in vivo electron spin resonance (ESR) has been used to follow the course of metabolism and distribution of a paramagnetic spin probe, 3-carboxamido-2,2,5,5-tetramethylpyrrolidine-1-oxyl. Sprague-Dawley rats (250-300 g) were catheterized in the jugular vein and given serial doses of the nitroxide spin probe above. The decrease in the tail blood nitroxide ESR spectrum with the time was followed. This reflects both normal distribution/excretion and a significant metabolic step--reversible reduction of the nitroxide group to its hydroxylamine. The studies serve as important and useful comparisons to the nitroxide reduction kinetics in vitro while offering the important advantage of avoiding those non-steady-state artifacts frequently expected in ex vivo procedures. This study represents the first report of systematic in vivo pharmacokinetics of a paramagnetic probe.