The response of genital and gonadal growth during the first year of treatment with human growth hormone (hGH) was studied in 20 boys with isolated growth hormone deficiency (IGHD) (11 of hereditary origin and 9 sporadic cases). Prior to hGH treatment, 13 of the 15 prepubertal boys had a penis length below the normal mean, 3 of which were more than 2 SDS below the mean. The boys with hereditary IGHD had a greater deficit in penile size than did the sporadic cases. hGH treatment improved the penile length in all but two boys aged 14 and 15 yr, and led to growth up to normal size in the three boys with very small penises. Three of the hereditary IGHD patients had subnormal testes and all of the other prepubertal boys had a testicular volume in the normal range. hGH treatment increased testicular size, particularly in the prepubertal boys. Of three additional untreated adults with IGHD, one had a subnormal-size penis and two had penises of low-normal size. Our findings constitute further evidence that hGH deficiency is associated with decreased penile growth and, to some extent, decreased testicular size, and that hHG treatment improves the growth of the genitalia and gonads. Since these effects were also observed in prepuberty, it seems that not all the hGH or, rather, somatomedin effect on sex organs is androgen mediated.