The influence of the initial L-T4 dose and some other factors on the intellectual development was evaluated at 7 years of age in 47 congenitally hypothyroid children detected by the regional screening program. All patients were initially treated with 25 micrograms LT4/kg/day that represented a mean replacement dose of 6.8 +/- 1.3 micrograms/kg. Despite the "low" initial dose mean IQ at 7 years resulted within normal range (96 +/- 9). Twenty-eight patients initially treated with 6.0 +/- 0.6 micrograms L-T4/kg/day had a mean IQ (96 +/- 9) which was not different with respect to 19 patients (IQ 94 +/- 7) treated with a significantly higher L-T4 dose (8.1 +/- 0.9 micrograms/kg/day; p < 0.0001). The initial L-T4, dose did not correlate with IQ at 7 years whereas a significant correlation was found between IQ and serum T4 concentration at diagnosis (r = 0.35; p < 0.01) regardless of the fact that serum T4 concentration normalized after the first 2 months of therapy in both groups. Twenty-three patients whose serum T4 at diagnosis was < 2 micrograms/dl (1.0 +/- 0.5) had a mean IQ at 7 years (92 +/- 9) which was significantly lower than the 24 patients (IQ 98 +/- 7; p < 0.02) whose serum T4 was > 2 micrograms/dl (5.7 +/- 2.4; p < 0.001). The present findings suggest that the severity of neonatal hypothyroidism is an important factor in determining subsequent intellectual development of congenitally hypothyroid children.