Pseudouridine (Ψ) is a unique nucleoside accumulated in the sera of renal failure (RF) patients. Surprisingly data on its excretion are lacking. To get an overview, the Ψ serum level and urinary excretion were investigated in 73 healthy subjects (C), 16 patients not on dialysis (ND) and 12 hemodialysis patients (D). It was found: (a) Ψ accumulates in the sera of both ND and D patients. An inverse power correlation fits best with the relationship between serum Ψ and the clearance of endogenous creatinine (CCr)· The amount of Ψ filtered in glomeruli of ND patients increases while it remains practically unchanged in D patients. However, the Ψ filtration load of residual nephrons increases with the decreasing CCr as a consequence of its increased serum concentration, (b) Both Ψ net resorption and secretion have been found in C subjects. The increased Ψ resorption diminishes the necessary increase of Ψ urinary excretion both in ND and D patients. The increase of Ψ resorption is marked if calculated on residual nephrons. (c) The slightly decreased Ψ excretion excludes the participation of its increased synthesis in its accumulation in RF. It is concluded that Ψ accumulation in RF is caused by the impairment of its kidney excretion and the increased Ψ resorption participates markedly in