Arachidonic acid metabolites, especially prostacyclin I2, are regulators of vascular tone, and may be released from contracting muscle. In the present study, the influence of exercise on accumulation of prostaglandins and thromboxane in skeletal muscle was determined by the use of microdialysis technique using PGE2-3H as an internal reference. Interstitial tissue concentrations were determined both in m. gastrocnemius during intermittent static exercise (protocol A, 40 min, perfusion rate: 1 microL min-1) as well as in m. vastus lateralis during dynamic knee extension (protocol B, 20 W, 60 min, perfusion rate: 3 microL min-1). Relative recovery always rose with transition from rest to exercise (82 +/- 8% (A) and 75 +/- 7% (B), respectively) and returned to basal values during postexercise. Interstitial PGE2 concentrations rose 4-fold with dynamic exercise (0.95 +/- 0.26 ng mL-1 (rest) to 3.97 +/- 0.75 (exercise), P <0.05), but where unchanged in response to intermittent static exercise. TXB2 decreased during intermittent static exercise, whereas intramuscular PGI2 (6-keto-PGF1alpha) concentration did not change with intermittent static exercise. The present study demonstrates measurable amounts of prostaglandins and thromboxanes in the interstitial space of skeletal muscle. Furthermore, the concentration of prostaglandin E2 is unchanged during static calf exercise and increased markedly with dynamic thigh muscle exercise, which together with an exercise induced increase in muscle blood flow indicate, that prostaglandin E2 is released from skeletal muscle during exercise in humans.