Growth acceleration and bone maturation were studied in children with severe short stature and a history of intrauterine growth retardation (IUGR) to determine the effect of growth hormone (GH)-treatment. Patients were enrolled in an open randomized, multicenter trial and allocated to either the treated group (group 1, n = 38) or the control group (group 2, n = 31). Both groups were treated daily with 0.2 IU/kg/body weight during 3 years. The children in group 2 started the study with a 1-year observation period followed by a 3-year treatment period. At baseline, the mean age was 4.5 years, bone age was 3.3 years, height standard deviation score (SDS) was -3.4, height velocity (HV) SDS was -1.6. Auxologic data were measured every 3 months and bone age was assessed at the start of the study (baseline) and then every 12 months thereafter. After 1 year of treatment, linear HV in group 1 increased significantly in comparison with the pretreatment period (from 5.7 +/- 2.0 to 10.1 +/- 1.7 cm/year; p < 0.001). Increased HV was sustained during the 2nd and 3rd year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3 years of growth hormone (GH) treatment in group 2. The mean height SDS for chronological age increased by 2.0 +/- 0.7 in the 2 groups after 3 years of treatment. Bone age remained retarded but increased with a mean of almost 4 years after 3 years of treatment in both groups. Even at a dose that is three times the replacement dose, treatment with recombinant human GH was well tolerated. From these results, we conclude that recombinant human GH treatment over 3 years can induce sustained catch-up growth in young children with severe short stature and a history of IUGR.