Hyaluronate, a glycosaminoglycan of connective tissue matrix, was measured in serum by radioassay in patients with renal insufficiency (n = 22) and with end-stage renal failure (n = 40). The serum hyaluronate levels were significantly increased in both groups compared with the levels measured in age- and sex-matched healthy controls. Significant correlations were found between serum hyaluronate and degree of impaired renal function. None of the patients had laboratory signs indicating affection of the liver, the major elimination route for circulating hyaluronate. No significant alteration of hyaluronate levels was seen during hemodialysis. Renal transplants, previously on dialysis treatment, had normal serum hyaluronate values. Data obtained indicate either an essential role of the kidneys for the elimination of circulating hyaluronate or an increased outflow of hyaluronate to the circulation in uremia or a combination of these two possibilities. The altered metabolism of hyaluronate in uremia was not only related to the azothemic state but also to the age of the patients. The mechanism may be qualitively similar to that underlying the age-dependent increase of serum hyaluronate seen in health. The hypothesis that elevated serum hyaluronate in uremia may reflect an accelerated ageing of the connective tissue is highly speculative, but has some support by the finding that cardiovascular and other clinical symptoms were linked to particularly high serum levels of hyaluronate.