Administration of androgens to adolescent boys with constitutional delay in growth has been highly controversial. One hundred forty-eight adolescent boys with constitutional delay of growth and puberty with a mean age of 14.3 +/- 0.7 years were treated with testosterone enanthate 100 mg intramuscularly each month for 6 months. Growth parameters, sexual maturation, and circulating concentrations of testosterone and insulin-like growth factor-I (IGF-I) were compared with those for 50 age-matched adolescent boys with constitutional delay of growth and puberty with a mean age of 14.1 +/- 0.9 years who did not receive any treatment. The mean height growth velocity, height standard deviation score, weight gain, and IGF-I concentration were significantly greater in the treatment group after 1 year of follow-up evaluation. The advancement in bone age equaled that in chronologic age in the treatment group, with no significant change in the bone age to chronologic age ratio (BA/CA) before versus after therapy. All subjects in the treatment group had clearly entered puberty by the end of 1 year. Testicular size increased significantly in the treatment group and they had significantly higher serum testosterone concentrations 6 months after the end of testosterone therapy as compared with the control group, denoting activation of the hypothalamic-pituitary testicular axis. All subjects in the treatment group were psychologically satisfied with the enhanced growth and increased muscle mass, versus only 40% of those in the control group. In conclusion, our regimen appears to be efficacious and safe for treatment of boys with constitutional delay of growth and puberty and has no deleterious effect on skeletal age.