A multicentre randomized trial of human growth hormone (GH) treatment was carried out in 121 children with short stature who did not meet the classic criteria for GH deficiency. In the first year of the trial, half of the children received treatment with recombinant somatropin 0.1 mg/kg (0.27 IU/kg) three times weekly and showed a significant increase in mean growth velocity from a pretreatment value of 4.6 +/- 1.1 to 7.5 +/- 1.2 cm/year (mean +/- SD). The growth velocity of the untreated children did not change significantly. The growth velocity of the control group (including 10 pubertal children) increased from 4.2 +/- 1.3 to 5.0 +/- 1.4 cm/year. In the second year, half of the control group received treatment with somatropin, 0.1 mg/kg (0.27 IU/kg) three times weekly, while the remainder received the same weekly dose on a once-daily basis. The mean growth velocity increased in both cases to 8.2 +/- 1.4 and 9.0 +/- 1.6 cm/year, respectively. The group treated during the first year was also divided into two groups in the second year. One group continued with the original treatment regimen, resulting in a mean growth velocity of 6.8 +/- 1.8 cm/year. The other group changed to once-daily treatment at the same weekly dose and the mean growth velocity for this group in the second year was 7.8 +/- 1.4 cm/year. The gain in height age in both of these groups exceeded the bone age in both the first and second years of treatment, suggesting a gain in predicted adult height.(ABSTRACT TRUNCATED AT 250 WORDS)