Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of the male reproductive system. Twenty-one days old ICR mice weaned from dams fed with a casein-based AIN-76A diet during gestation and lactation were exposed to genistein (2.5 and 5.0 mg/kg/day, p.o.) for 5 weeks. 17beta-Estradiol (7.5 microg/kg/day) and corn oil were used for the positive and negative vehicle controls, respectively. The animals were fed the casein-based AIN-76A diet throughout the experiment. There were no significant differences in body weights of mice between the genistein groups and the negative control group. No significant differences in relative reproductive organ weights were found among all experimental groups. Sperm counts in epididymis and testes were slightly decreased in the genistein-exposed groups compared with control group. Sperm motile characteristics in genistein-exposed groups were slightly higher than those of the control group. Levels of phospholipid hydroxide glutathione peroxidase mRNA in the testis, epididymis, and prostate of mice exposed to genistein or estradiol were significantly higher than those of the controls (P<0.05). Exposure to genistein caused hyperplasia of Leydig cells in the testis and a slight increase of interstitial fibroblasts in the epididymis, while estradiol treatment caused severe damage to the testis and epididymis. These results suggest that dietary uptake of genistein during the juvenile period may affect male reproductive development, resulting in a slight decrease in sperm count, but with an increase in sperm motion quality.