This study was carried out to evaluate the effects of an iv injection of parathyroid extract on serum levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D3] in elderly osteopenic patients and age-matched nonosteopenic controls. Serum concentrations of 1,25-(OH)2D were reduced in elderly osteopenic subjects (mean +/- SEM, 20 +/- 3 pg/ml) compared with values in age-matched nonosteopenic controls (35 +/- 3 pg/ml), whereas no differences were found in serum 24,25-dihydroxyvitamin D levels (1.5 +/- 0.3 and 2.2 +/- 0.5 ng/ml, respectively). An iv injection of parathyroid extract was followed by a significant increase in serum 1,25-(OH)2D levels in both osteopenic patients (16 +/- 6 pg/ml) and controls (15 +/- 5 pg/ml). The mean 4-h increases in serum 1,25-(OH)2D of 11-18 pg/ml were not significantly different in the two groups. The results indicate that the reduced 1,25-(OH)2D concentrations in the osteopenic patients are secondary to changes in factors that normally stimulate this enzyme system.