The exercise-induced increase and post-exercise decrease of plasma hyaluronan concentration were studied in human subjects. Six well trained men performed incremental exercise until exhaustion (MAX), intensive (submaximal, SUB) and extensive exercise (moderate, MOD) on a bicycle ergometer, defined as work at 100, 77 and 50% of maximal oxygen consumption. Hyaluronan was analyzed using a high-sensitivity, proteoglycan-dependent time-resolved immunoassay and hemoglobin, hematocrit and plasma protein levels were assessed using standard laboratory procedures. Compared to resting control levels, the plasma hyaluronan concentration (pHA) increased (p < 0.05) by 76% (65.0 +/- 6.1 vs. 37.0 +/- 1.0 microg/l) during 15 min MAX, by 44% (56.4 +/- 2.6 vs. 39.2 +/- 3.8 microg/l) during 30 min SUB and by 27% (46.3 +/- 7.8 vs. 36.4 +/- 4.3 microg/l) during 90 min MOD. The increase with time averaged 4.03%.min(-1) during MAX, 1.35%.min(-1) during SUB and 0.35%.min during MOD. After exercise (15 and 30 min), pHA decreased by 43% below resting levels after MAX (p < 0.05) and by 36% after SUB, respectively. In conclusion, pHA steadily rose with time during physical exertion, with a non-linear increase of concentration/time slope with exercise intensity; second, the magnitude of the post-exercise pHA decrease was proportional to the exercise-induced pHA increase, suggesting elevated hyaluronan clearance with rising plasma levels after physical exertion.