The plasma concentration of T-3 increases during the third postnatal week in rats when the young are weaned. Renal phosphate (Pi) transport matures during this period, with increases in the carrier affinity for Na-cotransported Pi (1/K-m) and in the maximal transport rate (V-max. As prevention of weaning prevents the normal increase in the plasma T-3 concentration and blocks the maturation of Pi trans port, this study examines the influence of T-3 on Pi transport maturation. The brush border membranes from 21-day-old rats rendered hypothyroid with 6-n-propyl-2-thiouracil (PTU) or prevented from weaning (PW) were examined. These two treatments effectively prevented normal maturation, as the apparent K-m was significantly higher in the PTU (0.243 +/- 0.04) and PW (0.159 +/- 0.008) rats than in controls [0.111 +/- 0.032 (n = 6; P < 0.05) and 0.104 +/- 0.005 (n = 6; P < 0.05)], and the V-max was significantly lower [3192 +/- 170 us. 4269 +/- 343 (n = 6; P < 0.01) and 3479 +/- 478 us. 4184 +/- 368 (n = 6; P < 0.05)]. Administration of T-3 to PTU and PW rats restored the apparent K-m and V-max, to central values. The amounts of Na-Pi cotransporter messenger RNA and protein were also determined. The amounts of NaPi-2 messenger RNA and protein were decreased about 5-fold in PTU and PW rats, and T-3 restored them to control levels. The effect of T-3 on the maturation of Pi transport was independent of PTH, GH, or glucocorticoids. Thus, thyroid hormone helps control the maturation of Pi transport in the rat during weaning, and thyroid hormone magi be a dominant triggering factor in this process.