Aims/hypothesis GW501516, an agonist of peroxisome proliferator-activated receptor-δ (PPAR-δ), increases lipid combustion and exerts antidiabetic action in animals, effects which are attributed mainly to direct effects on skeletal muscle. We explored such actions further in isolated rat skeletal muscle. Materials and methods Specimens of rat skeletal muscle were pretreated with GW501516 (0.01-30 μmol/l) for 0.5, 4 or 24 h and rates of fuel metabolism were then measured. In addition, effects on mitochondrial function were determined in isolated rat liver mitochondria.