Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.