The relationship between oestrogen replacement treatment and the risk of endometrial cancer was analysed in a case-control study of 158 histologically confirmed incident cases below the age of 75 and 468 controls in hospital for acute, non-neoplastic, non-hormone-related conditions conducted in the Swiss Canton of Vaud in 1988-1992. Overall, 60 (38%) cases vs. 93 (20%) controls had ever used oestrogen replacement treatment: the corresponding multiple logistic regression relative risk (RR) was 2.7 (95% confidence interval, CI: 1.7-4.1). The risk was directly related to duration of use, and rose to 5.1 (95% CI: 2.7-9.8) for > 5 year-use. The RR was still significantly elevated 10 or more years after stopping use (RR = 2.3, 95% CI: 1.2-4.5). When the role of covariates was considered, a significant interaction was observed with body mass index (RR for long-term oestrogen use = 6.0 for lean or normal weight women vs. 2.4 for overweight women). There was also a hint of a negative interaction with oral contraceptive (OC) use, since the RR for oestrogens was higher (or restricted) to women who had never used OC (RR = 5.4, for long-term oestrogen use), as compared with those who had used OC, who showed no significant evidence of association with oestrogens (RR = 0.9 for long-term use). There was no significant interaction with cigarette smoking. Thus, this study confirms the presence of a strong association between oestrogen replacement treatment and endometrial cancer risk, since in the late 1980s or early 1990s about 25% of cases could be attributed to oestrogen replacement treatment in this Swiss population. Further, it confirms the presence of significant negative interactions of oestrogen use with obesity, and, possibly, with OC as well.