The effect of oral Etoposide (VP‐16‐213) on the ovarian function in 22 patients with residual gestational trophoblastic disease was studied by serial weekly measurement of serum follicle stimulating hormone (FSH), 17β‐estradiol (E2), progesterone (P) and prolactin (PRL), and monitoring of the menstrual patterns during and after drug treatment. Multiple courses of VP‐16‐213 at a dosage of 200 mg/m2 × 5 days were given 1 week apart. Following an average dose of 5.0 gm, five young patients developed transient ovarian failure for a mean period of 2.4 months and two elderly patients developed permanent ovarian failure (total incidence, 7/22, 31.8%) as evidenced by hypergonadotropic, hypoestrogenic amenorrhea. In addition, two patients each developed anovulatory cycles and hypomenorrhea. VP‐16‐213 should therefore be regarded a potent gonadotoxic drug and these hitherto unreported side effects should be recognized when the drug is used in menstruating females.