The adaptive increase in renal proximal tubule 25-hydroxyvitamin D-alpha-hydroxylase activity (1-OHase) during dietary calcium restriction is mediated by an increase in parathyroid hormone (PTH) and is inhibited by aging. Recent studies in mature (3-4 mo) rats demonstrated that insulin-like growth factor-I (IGF-I) restored stimulation of renal 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] production by low phosphorus diet (LPD), another major stimulus of 1-OHase. These studies were designed to determine whether IGF-I stimulates 1-OHase during low calcium intake in old rats. Male rats were fed a normal calcium diet (NCD, 6 g Ca/kg diet) or low calcium diet (LCD, 0.2 g Ca/kg diet) for 14 d, and recombinant human IGF-I [rhIGF-I, 1.4 mg/(24h 160 kg body wt)] or vehicle was administrated via miniosmotic pump for 72 h before killing. In 4-mo-old male Sprague-Dawley rats, LCD increased in vitro renal 1-OHase activity in the presence but not in the absence of rhIGF-I. LCD increased in vitro1-OHase activity in young (1-mo-old) but not old (24-mo-old) male Fischer 344 rats. RhIGF-I increased 1-OHase activity in 24 mo-old rats fed LCD to levels that were not different from those in 1-mo-old rats fed LCD. The results indicate that the adaptive increase in 1-OHase activity due to a LCD is lost by 4 mo in rats and can be restored by pharmacologic doses of rhIGF-I.