Height reduction by means of treatment with high doses of sex steroids in constitutionally tall stature (CTS) is a well known, though still controversial, therapy. The establishment of the effect of such therapy is dependent on the height prediction method applied. We evaluated the reliability of various prediction methods together with the subjective clinician's judgment in 143 untreated children (55 boys and 88 girls) with CTS and the effect of height-reductive therapy in 249 tall children (60 boys and 159 girls) treated with high doses of sex hormones (cases). For this purpose, we compared the predicted adult height with the attained height at a mean adult age of 25 yr and adjusted the therapeutic effect for differences in bone age (BA), chronological age (CA), and height prediction between untreated and treated children. At the time of the height prediction, controls were significantly shorter, had more advanced estimated BAs (except for the BA according to Greulich and Pyle in boys), had lower target heights, and had smaller adult height predictions compared with the CTS patients (P < 0.05). At the time of the follow-up, CTS patients were significantly taller than controls for both boys and girls (P < 0.02). In controls, a large variability was found for the errors of prediction of the various prediction methods and in relation to CA. The prediction according to Bailey and Pinneau systematically overestimated adult height in CTS children, whereas the other prediction methods (Tanner-Whitehouse prediction and index of potential height) systematically underestimated final height. The mean (SD) absolute errors of the prediction methods varied from 2.3 (1.8) to 5.3 (4.3) cm in boys and from 2.0 (1.9) to 3.7 (3.5) cm in girls. They were significantly negatively correlated with CA (r = [minus 0.27 to -0.65; P < 0.05), except for the Tanner-Whitehouse prediction in boys, indicating that height prognosis is more reliable with increasing CA. In addition, experienced clinicians gave accurate height predictions by evaluating the growth chart of the child while taking into account various clinical parameters, such as CA, BA, and pubertal stage. The effect of sex hormone therapy was assessed by means of multiple regression analysis while adjusting for differences in height prediction, CA, and BA at the start of therapy between treated and untreated children. The mean (SD) adjusted effect varied from -0.5 (2.4) to 0.3 (1.4) cm in boys and from -0.6 (2.1) to 2.4 (1.4) cm in girls. The adjusted height reduction was dependent on the BA at the time of start of sex hormone therapy and was more pronounced when treatment was started at a younger BA. In boys, the treatment effect was significantly negative at BAs exceeding 14-15 yr. After cessation of therapy, additional mean (SD) growth of 2.4 (1.2) and 2.7 (1.1) cm was observed for boys and girls, respectively. The mean (SD) BA according to Greulich and Pyle at that time was 17.1 (0.7) yr for boys and 15.2 (0.6) yr for girls. These data demonstrate that height prediction in children with CTS is inaccurate in boys, but clinically acceptable in girls. With increasing age, height prognosis became more accurate. Overall, the height-reducing effect of high doses of sex hormones in children with CTS was limited, especially in boys. However, a significant effect of treatment was observed when treatment was started at BAs less than 14-15 yr, depending on the method of BA assessment. In boys, treatment appeared to be contraindicated at BAs older than 14-15 yr, because androgen administration caused extra growth instead of growth inhibition. It is recommended that referral should take place early, preferably before puberty, for careful monitoring of growth and height prediction. Moreover, it is recommended not to discontinue therapy before complete closure of the epiphyses of the hand has occurred to avoid considerable posttreatment growth.