Target tissue 1,25-dihydroxyvitamin D [1,25-(OH)2D] receptor was monitored in adult (15- to 18-month-old) and young (4- to 5-week-old) male Holtzman rats. The concentration of unoccupied receptor (femtomoles per mg protein) was significantly higher in the intestine (666 +/- 19 vs. 162 +/- 43) and bone (61 +/- 3.7 vs. 18 +/- 2.5) of young rats compared to that in adults. The dissociation constant (Kd) of the intestinal receptor, however, remained very similar at both ages (young, 0.24 nM; adult, 0.53 nM). A similar age-related decline in unoccupied intestinal receptor was also observed in Fischer 344 rats and cows. Infusion of young and adult Holtzman rats with about 72 ng/kg BW 1,25-(OH)2D3 resulted in similar changes in the concentrations of plasma 1,25-(OH)2D3 (150-160 pg/ml) in both age groups. The 1,25-(OH)2D3 infusions also resulted in significant up-regulation of unoccupied intestinal receptor (femtomoles per mg protein) from 512 +/- 27 to 780 +/- 61 in the young rats and 68 +/- 9.4 to 194 +/- 15 in the adult rats. Receptor up-regulation by 1,25-(OH)2D3 (change from control) was significantly higher (P less than 0.05) in young rats (268 +/- 51 fmol/mg protein) than in adults (125 +/- 8.2 fmol/mg protein). These data suggest that the differences in receptor number in young and adult rats may be responsible for functional changes in target tissue response to 1,25-(OH)2D3 associated with advancing age.