Unopposed oestrogen replacement therapy increases the risk of endometrial cancer in post-menopausal women. However, the addition of progestogen to the oestrogen therapy reduces the risk of endometrial carcinoma by preventing and effectively treating hyperplasia of the endometrium. In a 5-yr prospective study with a further 4 yr of follow-up (1975-83), 31 adenocarcinomas of the endometrium were detected over 27243 patient-years of observation, for an incidence of 113.8:100 000 women. The first report on the results of the study appeared in 1978; this paper presents further results. The lowest incidence of endometrial cancer (49.0:100 000) was observed among the oestrogen-progestogen users and the highest (390.6:100 000) among the unopposed oestrogen users. Not only was the incidence of endometrial carcinoma significantly lower in the oestrogen-progestogen users than in those using unopposed oestrogens (P less than or equal to 0.0001), but it was also significantly lower than that among the non-hormone users (245.5:100 000 with P less than or equal to 0.0005). Endometrial hyperplasia had been diagnosed previously in 12 of the 31 patients with adenocarcinoma (38.7%) from 4 mth to 8 yr before the detection of cancer. When given for 7-10 days each month progestogens are effective in reversing hyperplasia and restoring a normal endometrium in 94.5% of patients treated within 3-6 mth. The progestogen challenge test was devised to identify post-menopausal women at greatest risk for adenocarcinoma of the endometrium. It is concluded that the use of this test will reduce the risk of endometrial cancer in both oestrogen-treated post-menopausal women and women with increased endogenous oestrogens.