This study examined the effects of thyroxine (T-4) treatment on spatial learning and memory in congenitally hypothyroid (CH) rats. Forty CH male offspring of methimazole-treated dams were randomly divided into three groups: no T-4 (vehicle) treatment (n= 12), T-4 treatment commencing on postnatal day (P-) 7 (n = 14), and T-4 treatment commencing on P-21 (n = 14). Normal male rats were used as a control group (it = 14). T4 was administered daily (sc, 0.02 mu g/g) to the treatment groups for 30 days. A water-maze was used to assess behaviour at 42, 70 and 98 days of age. T-4 treatment beginning at P-7 improved learning and memory associated with CH at 70 and 98 days of age but T-4 treatment beginning at P-21 did not improve CH-impaired learning and memory. (C) 2007 Elsevier Inc. All rights reserved.