Previous studies have reported inconsistent results regarding the modifying effect of hormone replacement therapy (HRT) on the association of body mass index (BMI) and the risk of colorectal cancer (CRC) among postmenopausal women. We assessed the use of HRT and BMI in 208 postmenopausal women with histologically confirmed incident CRC and 246 controls in a population-based case-control study in Germany (DACHS study). Ever use of HRT was strongly associated with reduction of CRC risk (adjusted odds ratio 0.41, 95% confidence interval 0.25-0.67). Among nonusers of HRT, risk of CRC was strongly increased in women with BMI 27 to <30 kg m(-2) (2.76, 1.07-7.12) and obese women (3.30, 1.25-8.72), when compared with women with BMI <23 kg m(-2) (P for trend <0.01). BMI was not associated with risk of CRC among HRT users (P for interaction <0.01). In contrast to most other studies, a positive association of BMI and CRC risk was found among nonusers of HRT, but not among users of HRT. The reasons for the inconsistency of results regarding the potential risk modifying effect of postmenopausal hormones in the association of BMI with CRC remain inconclusive and require further study.