As part of a collaborative project to determine the minimum administration period to detect compound effects on male reproductive organs in Sprague-Dawley (Crj:CD(SD)) male rats, 6- and 8- week-old rats were administered ethylene glycol monomethyl ether (EGME) daily at 100 and 200 mg/kg/day for 2 weeks or 100 mg/kg/day for 4 weeks, and histopathological changes in the testes and epididymides were examined. Testis and epididymis weights in the 2-week 200 mg/kg and 4-week 100 mg/kg groups were obviously decreased. On histopathological examination, severe degenerative changes in the testis such as atrophy of the seminiferous tubules and multinucleated giant cell formation were observed in all 2-week 200 mg/kg group rats. Degeneration of pachytene spermatocytes in Stages X IV-II, III and a decrease in the number of germ cells was observed with both 2 and 4 weeks treatments at 100 mg/kg/day. In the epididymides, the number of sperm in the caput decreased with 100 mg/kg/day groups after both 2 and 4 weeks. In addition, degeneration of pachytene spermatocytes induced by EGME was found to be exclusively due to apoptotic death. Similar testicular and epididymal changes were observed with 2 and 4 weeks treatments at 100 mg/kg/day of EGME. Therefore, we conclude that a 2 weeks administration period is sufficient for detection of EGME effects on male reproductive organs.