In patients with a moderate degree of renal insufficiency, restriction of dietary phosphate suppresses PTH secretion by increasing serum calcitriol. However, this may not operate in advanced renal failure. The present study was designed to evaluate the influence of serum phosphate levels on PTH secretion in oral 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] pulse therapy. 22 patients with secondary hyperparathyroidism [carboxy-terminal PTH (c-PTH) concentration: 19.5+/-13.9 ng/ml, mean +/-SD] received oral doses of 1,25(OH)2D3 (3.0-4.0 micrograms) twice a week, each at the end of hemodialysis, for 12 weeks. Doses of phosphate binders remained unchanged throughout this period. Patients were divided into two groups: group A (11 subjects) with mean serum phosphate levels of less than 6.0 mg/dl and group B (11 subjects) with levels of 6.0 mg/dl and above. There was no significant difference in the average corrected serum calcium levels. The reduction in serum intact PTH levels was greater in group A than in group B. A negative correlation (r = -0.48; p < 0.05) was observed between mean serum phosphate levels and the percent decrease in serum c-PTH levels. The findings of this study indicate an important role for dietary phosphate reduction in oral 1,25(OH)2D3 pulse therapy and suggest that serum phosphate reduction may play a part in suppressing PTH secretion through a mechanism independent of 1,25(OH)2D3 and plasma calcium levels.