The incidence of gouty arthritis and the role of renal urate handling and diuretic use were studied in 85 cadaveric kidney graft recipients with a graft functioning for at least two years. The incidence of gout was 24% in patients using cyclosporine (CsA, n = 55); no patient using azathioprine (Aza, n = 23) had gout. In patients using CsA, the fractional urate clearance decreased between 1 and 3 months after transplantation, thereafter remaining stable at a significantly lower level than in patients using Aza, pointing toward a specific effect of CsA on tubular urate handling. This impaired fractional urate clearance was not reversible up to 18 months in 7 patients after conversion from CsA to Aza, suggesting irreversible tubular damage. Multiregression analysis showed that the impaired fractional urate clearance and the use of furosemide were significant contributors to the occurrence of gout in patients using CsA.