Plasma homocysteine in three different groups of patients with chronic renal failure (one group without dialysis, one with CAPD and one with hemodialysis) was increased compared to controls. Another group of patients with slightly reduced renal dysfunction (normal serum creatinine but reduced glomerular filtration rate) did not, however, show increase of plasma homocysteine. The clearance of homocysteine as a percentage of creatinine clearance in the three different groups of patients with chronic renal failure was also significantly increased compared to controls. Thus the clearance of homocysteine was not affected to the same extent as that of creatinine in renal failure. This may be attributed to the fact that, besides the reduced glomerular filtration rate, a depressed tubular uptake of homocysteine may occur in chronic renal failure. We were also able to show that neither in patients with varying renal function nor in controls were there any significant diurnal variation of plasma homocysteine, despite the intake of a protein-rich meal. However, after methionine loading in eight patients with severe chronic renal failure, a slight but significant increase of plasma homocysteine was noted. This indicates a disturbed metabolism with high amounts of homocysteine, which might be mainly attributed to an impaired transulphuration pathway.