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The capacity of bone to organize and reorganize its structure in response to changing mechanical demands is well recognized. However, the mechanism by which the changing mechanical environment is detected, and the means by which this information is translated into a stimulus for structural modification, are not understood. A group of substances suggested to be involved in the initial transduction of strain information are the prostaglandins. In this experiment we used a single period of dynamic loading to stimulate an adaptive osteogenic response in vivo. Loading was performed in the presence and absence of indomethacin. Measurements of the periosteum 5 days after loading showed that the presence of indomethacin at the time of loading reduced the osteogenic response. Though consistent with the hypothesis that prostaglandins are involved in the initial transduction of tissue strain into a biochemical response, this result is not sufficient to demonstrate this conclusively because reduced prostaglandin levels during the 24 hours immediately after the period of loading may affect many other points in the cascade of events between strain transduction and adaptive new bone formation. Furthermore, indomethacin at the relatively high levels we used (40 mg/kg) may have effects other than those on prostaglandin synthesis.