Prostaglandins are known to be involved in the regulation of local blood flow within human skeletal muscles during exercise, and the concentration of prostaglandins increases locally and systemically in response to exercise. The systemic release of prostaglandins can be inhibited by oral intake of non-steroidal anti-inflammatory drugs (NSAIDs). However, to study the local role of prostaglandins, the formation of prostaglandins within the tissue must be controlled. Microdialysis enables determination of local concentrations of water-soluble substances within the tissue. In the present study the microdialysis method was used to infuse NSAIDs locally into human skeletal muscles producing a local block of prostaglandin formation. In addition the graded blockade at various distances from the infusion site within the muscle during rest, exercise and recovery was determined. Microdialysis was performed in thigh muscles (m. vastus lateralis) in six healthy men. One of the microdialysis catheters was used to block prostaglandin synthesis by infusion of the NSAID indomethacin. Additional catheters were placed 1 and 4 cm away from the infusion and in the contralateral leg (control). Following 2 hrs rest, the subjects performed 200 maximal eccentric contractions with each leg followed by 3 hrs rest. The study revealed that infusion of NSAID reduced local prostaglandin E₂ concentration by approximately 30-50% (4 cm away from the infusion) and 85% (1 cm away from infusion) compared to the contralateral (control) thigh muscle. In conclusion, the present study shows that infusion of NSAIDs into human muscle via microdialysis catheters results in a graded blockade of prostaglandin synthesis.