In this study, we have investigated plasma pyridoxal 5'-phosphate (PLP) concentrations in undialyzed and dialyzed uremic patients and in kidney transplant subjects, using an enzymatic technique with thermal deproteinization to liberate PLP from plasma proteins. The specificity of the reaction indicates no interference with pyridoxal and only 3% interference with pyridoxamine phosphate. In 17 hemodialyzed patients, a deficiency of about 50% of plasma PLP concentration is found as compared to 25 healthy subjects (22.2 +/- 2.47 vs. 48.8 +/- 3.00 nmol . l-1), as mean +/- SEM). In seven undialyzed uremic patients with end-stage renal failure, the plasma PLP concentration is also decreased (29.3 +/- 1.74 nmol . l-1). The absence of PLP in plasma ultrafiltrates demonstrates that no loss of PLP occurs due to hemodialysis. The daily oral supplementation with 250-750 mg pyridoxal induces a supraphysiological increase in plasma PLP concentration in hemodialyzed as well as in undialyzed patients. In 116 non-uremic kidney transplant subjects, the mean plasma PLP concentration was 33.8 +/- 3.50 nmol . l-1). In 65% of these patients, a marked deficit (below 20 nmol . l-1) was observed. In conclusion, uremic patients have a deficient vitamin B6 state. Its correction with pyridoxal to restore physiological plasma PLP concentration necessitates oral supplementation with lower doses that those widely used at present. In kidney transplant patients a similar plasma PLP deficiency is observed in the absence of chronic renal failure.