The present study was aimed at answering the following two questions: (1) What is the effect of high dose vitamin D treatment on the serum level of 25-hydroxyvitamin D (25-OH-D) in patients with chronic renal failure (CRF)? (2) Is there any effect of urinary protein loss on the serum 25-OH-D levels during treatment with pharmacological doses of vitamin D? 42 patients with CRF were studied. They were treated conservatively by a low protein diet and received 15 mg of vitamin D2 once a week. Long-term administration of vitamin D caused a significant (5- to 7-fold) increase of plasma 25-OH-D level irrespective of the degree of proteinuria. This increase was noted only during the first 5 months of vitamin D2 treatment. Surprisingly only in some patients moderate hypercalcemia (> 2.75 mmol/l) was found. From the results obtained it is concluded that (1) patients with CRF differ from normal subjects in handling of high doses of vitamin D and (2) high dosage treatment with vitamin D may prevent hypocalcemia in patients with CRF in spite of high proteinuria.