High body mass index (BMI) has consistently been associated with increased colon cancer risk in men, but not in women. It is hypothesised that menopause-related changes in oestrogen levels play a role in gender-specific risk patterns. Most studies have been conducted in Western countries, where high incidence rates are coupled with a high prevalence of obesity and relatively common use of hormone replacement therapy (HRT) in post-menopausal women. This study evaluated the correlation between body mass index (BMI) and colon cancer risk in a relatively lean population, comprising 931 cases and 1552 controls, in Shanghai, China, where HRT use was extremely rare among women, during 1990-1993. Among men, colon cancer risk significantly increased with increasing BMI (P-trend=0.005). Among women, the risk varied with age and menopause status in a similar pattern. Within each menopause stratum, however, the BMI-related risk was similar for those aged under 55 years and those aged 55 years and over, indicating a menopause rather than age effect. Among pre-menopausal women, the odds ratios (ORs) for subjects in the highest versus lowest quintile were 1.9 (95% CI 1.1-4.9) for those under 55 years of age, and 2.2 (95% CI 1.4-8.2) for those aged 55 years and over. Among post-menopausal women, the corresponding ORs were 0.6 (95% CI 0.5-0.91) and 0.7 (95% CI 0.5-0.95), respectively. Our findings suggest that BMI predicts colon cancer risk in both genders. Among women, however, the risk is modified by menopause status, possibly through altered endogenous oestrogen levels.