Eight-seven cases of secondary amenorrhoea of more than 6 months' duration developing after treatment with oral contraceptives (group I) were compared with 227 cases of secondary amenorrhoea not preceded by treatment with combined tablets (group II). The two groups were collected during the same period. The average age of the patients was 4 years higher in group I than in group II. Oligomenorrhoea and previously occurred in 30% of group I and in 46% of group II. Pronounced predisposing factors., such as psychogenic trauma and stress with or without considerable change in body weight, were encountered in 26% in group I and 56% in group II. The incidence of increased urinary output of 17-keto steroids, 17-ketogenic steroids and of hirsutism was slightly higher in group II. The percentage of eosinophilic cells in vaginal scrapings was low in 20% in group I as compared with 46% in group II. Spontaneous return of pituitary-ovarian function occurred in 40% in both groups. Patients recovering spontaneously in group I presented a maximum during the first few months, followed by a steady and fairly uniform decline. Spontaneous recovery in group II was more or less independent of time. It seems reasonable to believe that oral contraceptives did promote or contribute to the development of secondary amenorrhoea in about 50%, representing cases with various predisposing factors. A causal relation between oral contraceptives and secondary amenorrhoea was indicated in the remaining 50% because of perfectly normal ovarian function before treatment and absence of predisposing factors.