We have evaluated the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) in the presence of increased lactate levels induced by short-term heavy exercise. Five healthy male subjects received 159 MBq (+/- 13 MBq) 123I-BMIPP at rest and a week later after they performed a maximal exercise test using a bicycle ergometer. Planar and tomographic images were obtained with a dual-head gamma camera up to 4 h after administration of the tracer. Multiple blood samples were taken at different time points for blood clearance, substrate concentration measurements and for HPLC analysis of metabolites. The exercise test did not alter plasma glucose and non-esterified fatty acid concentrations, but blood lactate increased from 1.12 mmol/l at rest to 9.26 mmol/l with maximal exercise. After exercise, BMIPP showed a significantly faster plasma clearance than at rest and the production of PIPA, the end metabolite of BMIPP oxidation, was reduced. Activity in the heart was similar after exercise and at rest on planar images 15 min after injection (4.83 +/- 0.50% ID vs 4.80 +/- 0.43% ID, P = NS), although the myocardium-to-cavity activity ratio, as determined on the SPET images 20 min after tracer injection, was slightly increased after the exercise test (4.20 +/- 0.63 vs 3.78 +/- 1.34 at rest, P = NS). Significantly increased activity was observed in a leg muscle region of interest after exercise (4.98 +/- 0.50% ID vs 3.93 +/- 0.44% ID at rest, P = 0.02). Between early and late images, tracer washout from the myocardium increased from 20.72% at rest to 36.72% after exercise (P < 0.05), but was unchanged for liver and leg muscles. The metabolic and physiological alterations induced by exercise do not degrade image quality of BMIPP scintigraphy. On the contrary, exercise-induced hyperlactatemia seems to enhance myocardium-to-cavity activity ratios on SPET images, although this effect does not reach statistical significance in this small group of normal subjects. These findings further support the robustness of BMIPP SPET in varied metabolic environments.