We measured serum 1,25-dihydroxyvitamin D concentrations in 18 patients with renal cell carcinoma-associated hypercalcemia. Only 2 patients (11%) had low serum 1,25-dihydroxyvitamin D (less than 15 pg/ml) levels, and the mean 1,25-dihydroxyvitamin D level in the 18 patients was 44 +/- 30 (+/- SD) pg/ml, not different from the value of 42 +/- 22 pg/ml in 75 age-matched normocalcemic patients with various malignancies. Eighty-seven percent (26 of 30) of the hypercalcemic patients with extensive skeletal metastases due to other malignancies or with hematological malignancies had suppressed serum 1,25-dihydroxyvitamin D levels (less than 15 pg/ml). In hypercalcemic patients with other malignancies and no skeletal metastases, only 54% (21 of 39) had low serum 1,25-dihydroxyvitamin D levels. The mean serum 1,25-dihydroxyvitamin D level in the latter group was 21 +/- 26 pg/ml, significantly lower than that in normocalcemic patients. In renal cell carcinoma-associated hypercalcemia, suppression of circulating 1,25-dihydroxyvitamin D concentrations is uncommon.