The contralateral uninjected hind paws of rats which had been injected with Freund's complete (FCA) or incomplete (FIA) adjuvant 10,14, 18, or 22 days previously were perfused under urethane anaesthesia using a stainless steel coaxial catheter. In one series of experiments cyclic AMP (cAMP) levels were determined after a 2-hour perfusion. cAMP levels were also determined in rats treated on days 16-22 with either prostaglandin E(1) (PGE(1)) (500 mug/kg per day subcutaneously) or saline. When compared with control rats injected with FIA, after 22 days, cAMP levels in FCA-injected rats fell between days 10 and 18 and then rose between days 18 and 22. After PGE(1) treatment, paw volume on day 22 increased in rats injected with FCA, but cAMP levels were not significantly altered when compared with day 22 FCA-injected controls treated with saline. In a second series of experiments, using a slightly modified perfusion method, PG levels in extracts of 30-minute perfusates were determined after chromatography and bioassay. Protein levels and paw volume were also measured. No PGF was detectable in any perfusate. Changes in PGE levels in FCA-injected animals paralleled changes in paw volume, increasing from day 14 and reaching a maximum on day 22. Both parameters remained unchanged in FIA-injected rats. Protein levels in perfusates from FCA-injected animals were significantly greater than FIA-injected controls only on day 22. We suggest that the early changes in cAMP reflect the infiltration of activated leucocytes into the inflamed joint and that the increase in PGE is attributable to lysosomal enzyme activity. Later increases in cAMP are attributable both to the increasing PGE levels and to other changes in cellular activation. We suggest that high levels of PGE contribute to tissue damage which is reflected in raised protein levels.