It is surmised that studies on the relationship between the endocrinological milieu and therapeutic efficacy in male infertile patients are essential in elucidating the etiology of this disease and devising effective therapeutic methods. The relation between serum gonadotropin level and therapeutic efficacy has already been reported. In the present study, we investigated the basal levels of two sex steroids, i.e., testosterone and estradiol, and the estradiol:testosterone (E2/T) ratio, and also the increases in these parameters after the administration of hCG to human subjects presenting various degrees of testicular dysfunction, e.g., male infertile patients, aged males, Klinefelter's syndrome and hypogonadotropic hypogonadism. Special attention was given to the characteristics of the reserve capacity for secretion of estradiol in male infertile patients. The hCG test was performed on a total 527 subjects, including 65 normal adult males. The reserve capacity for the secretion of estradiol was investigated on the basis of the increasing rate in the serum E2/T ratio. The increasing rate in the serum E2/T ratio was statistically larger in subfertile males, oligozoospermia and azoospermia in comparison with the normal adult males. On the other hand, the aged males did not show any difference from the normal adult males, whereas the results were significantly lower in the male subjects with Klinefelter's syndrome and hypogonadotropic hypogonadism. It was considered that the increase in the serum E2/T ratio is one characteristic of the gonads of male infertile patients. The results of multiple regression analysis showed that the LH level, the pretreatment sperm concentration and the increasing rate in the serum E2/T ratio were important factors determining the increase in the sperm concentration after treatment. Accordingly, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less and a sperm concentration of 5 x 10(6)/ml or more, the relationship between the increasing rate in the serum E2/T ratio and therapeutic efficacy was investigated. It was found that the increasing rate in the serum E2/T ratio was significantly greater in the therapeutically ineffective cases compared with the therapeutically effective cases. On the basis of this finding, it was surmised that the percentage increase in the serum E2/T ratio is one index reflecting testicular function. In addition, for cases of oligozoospermia characterized by an LH level of 13.7mIU/ml or less, a sperm concentration of 5 x 10(6)/ml or more and the increasing rate in the serum E2/T ratio of 4.01 or less, the relationship between the degree of spermatogenesis and therapeutic efficacy was investigated.(ABSTRACT TRUNCATED AT 400 WORDS)