In this study, the experiments were designed to examine if Toki-Shakuyaku-San (TSS) has a neuroendocrine effect on ovulation. TSS (500 mg/kg Bwt in drinking water) was given to Sprague Dawley immature female rats on 25 days of age and during experimental sessions. Fifteen IU of the hMG (Gonadoryl 4; GNR 4) was injected intraperitoneally on the morning of 28 days of age, and avulation occurred in 70% of rats on the following day. In TSS drinking immature female rat, administration of GNR 4 on 28 days of age results in ovulation twice: once on 29 days of age and again on 31 days of age. Administration of sodium pentobarbital (Nembutal) at 12:30 pm on 28 days of age did not block the first ovulation on 29 days of age, but administration at 12:30 pm on 30 days of age blocked the second ovulation on 31 days of age. However, delayed ovulation was observed on 32 days of age. This evidence indicates that GNR 4 acts on the ovary directly and induces first ovulation in TSS treated rats. However, TSS treatment modulates the chain of events in the neuroendocrine control of ovulation and results in the second ovulation.