We evaluated the possible influence of physical activity on serum levels of hyaluronic acid (HA), plasma levels of elastase, and serum levels of procollagen III peptide. In 15 healthy individuals, HA increased from 26 +/- 9 micrograms/liter (mean +/- SD) before arising from a night's sleep to 54 +/- 24 micrograms/liter 1 hour after arising and performance of normal morning activities (P less than 0.001). HA in 14 patients who had inflammatory arthritis increased from 124 +/- 104 micrograms/liter to 402 +/- 232 micrograms/liter under the same conditions (P less than 0.001). The elevation due to physical activity was significantly (P less than 0.001) higher in patients with rheumatoid arthritis (RA) than that found in controls. A slight increase of HA in the afternoon was also observed in healthy subjects who performed heavy exercise, but a marked increase was seen in RA patients who performed moderate exercise. In another group of 24 RA patients, a more standardized blood sampling was performed before arising and during normal morning activities. An increase in HA was significantly (P less than 0.001) correlated to the synovitis mass, estimated by the Ritchie articular index. Maximum increases of HA were seen 30 and 60 minutes after arising; thereafter, levels decreased to those measured at rest. During the morning activities, procollagen III peptide remained stable, while plasma elastase tended to increase. It is proposed that HA, produced in the joint tissue structures and accumulated at rest, is carried by the lymph vessels to the general circulation during physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)