Insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 and 3 (IGFPB-1, IGFPB-3) are expressed in normal and neoplastic endometrium. Their role and the role of insulin in the aetiology of endometrial cancer, is unclear. We performed a population-based case-control study in Sweden, including 288 endometrial cancer patients and 392 control women and analysed total serum IGF-I, IGFBP-1, IGFBP-3, insulin and BMI levels stratified by disease and hormone replacement therapy status (HRT). Non-parametric statistical tests and logistic regression analyses were performed to assess associations with endometrial cancer. There were no substantial differences between the mean serum levels of IGF-I between cases (115.5, s.d. 61.3) and controls (110.6; s.d. 50.4; Wilcoxon P=0.84), or between subgroups of women classified according to other risk factors for endometrial cancer. There were no trends of increasing risk according to quartiles of IGF-I, IGFBP-1, IGFBP-3 and insulin serum levels. There was an increasing risk of endometrial cancer according to the serum levels of IGFBP-1, which was observed only among women who had ever used HRT. Serum IGF-I, IGFBP-1, IGFBP-3 and insulin levels seem unrelated to endometrial cancer risk. Among users of HRT, increasing IGFBP-1 levels seem to increase endometrial cancer risk.