Ischaemic contraction of skeletal muscle increases the venous concentration of adenosine. The present investigation was undertaken to determine changes in blood flow and the release of adenosine into venous blood resulting from 5 min of free flow contractions of the isolated gracilis muscle in dogs anaesthetised with pentobarbitone sodium (42 mg.kg-1) and artificially ventilated. Arterial and venous concentrations of adenosine were measured by high performance liquid chromatography. Five-minute-contractions (induced electrically, 6 V, 1.8 ms, 4 Hz) caused significant increases in blood flow (to 304 +/- 33% of control; mean +/- SEM, n = 9) and venous plasma adenosine concentration (from 126 +/- 18 nM to 293 +/- 76 nM, equivalent to an average increase in release of 7.28 +/- 1.89 nmol.min-1 100 g-1 wet weight of muscle). The venous oxygen tension decreased from 8.33 +/- 0.48 to 3.39 +/- 0.31 kPa (62.5 +/- 3.6 to 25.4 +/- 2.3 mm Hg). This small but significant increase in venous adenosine concentration within the vasoactive range, in the face of a concomitant increase in blood flow, suggests that an increase in the interstitial adenosine concentration during free-flow exercise may contribute to the total dilatation of the resistance vessels to increase blood flow and keep its own concentration low. A significant correlation between venous adenosine concentration and vascular conductance is therefore absent. The results suggest that adenosine may contribute to sustained active hyperaemia in skeletal muscle.