Serum thyrotropin concentrations are frequently elevated during treatment of children with congenital hypothyroidism. It is unclear if elevated thyrotropin during early treatment indicates non-optimal treatment. In a cohort of 49 children with congenital hypothyroidism, we studied the decline in serum thyrotropin concentration after initiating L-thyroxine treatment, the relationship between elevated thyrotropin and treatment variables, and non-compliance with the treatment as a possible cause of elevated thyrotropin. The initial mean dose of thyroxine was 8.5 (SD 3.3) micrograms/kg body weight/day: 71% of the serum samples obtained 15-21 days after the start of treatment had serum thyrotropin concentrations < 10 mU/l. Six children had no samples with serum thyrotropin < 10 mU/l during the first 3 months of treatment. These children had a lower thyroxine dose prescribed, and serum thyrotropin was normalized when the dose was sufficiently increased. During treatment, from 6 weeks of age, serum thyrotropin > 10 mU/l was related to a lower dose of thyroxine and lower serum thyroxine, and was not due to non-compliance with treatment.