The effect of treatment with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) and different diets on uremic arterial disease was studied. Three groups of rabbits with chronic renal failure (CRF) were kept on three diets with a low, medium or high content of calcium and phosphate. Half the rabbits in each group were treated for 18 weeks with 1 alpha-OH-D3, 0.02 micrograms/kg/day, without any significant changes in the serum concentrations of calcium or phosphate compared to placebo treatment. In the thoracic aorta, the content of calcium and phosphate was significantly increased in placebo-treated CRF rabbits on medium and high calcium and phosphate intakes compared to rabbits with normal renal function (p less than 0.05). The cholesterol content was unchanged. Treatment with 1 alpha-OH-D3 caused a further increase in the aortic content of calcium and phosphate in the CRF rabbits on medium and low calcium and phosphate intakes (p less than 0.05). No increase in the aortic cholesterol content was observed. The histological changes in the abdominal aorta consisted of medial proliferations with calcifications and intimal proliferations. The severity of these changes paralleled the mineral content of the thoracic aorta. Aggravation of uremic arterial disease may be a hitherto unrecognized side-effect of treatment with 1 alpha-OH-D3 in CRF.