Obesity is associated with increased cardiovascular disease risk factors in some, but not all, individuals, and blood pressure responses to weight loss are also heterogeneous. The purposes of this study are: (i) to assess associations among cardiovascular disease risk factors in obese individuals and (ii) to determine clinical predictors of a hypotensive response to weight loss. The study was undertaken in 155 consecutive patients enrolled in a weight loss programme. Individuals entering the programme were predominantly women and differences were found between men and women who joined the programme. Before weight loss, obese men exhibited higher cardiovascular disease risk factors (body mass indices, waist-to-hip ratios, systolic and diastolic blood pressures, serum glucose, and lower HDL cholesterol) than did women. However, among women, but not men, cardiovascular disease risk factors clustered in individuals with higher waist-to-hip ratios. Furthermore, in contrast to men, a higher waist-to-hip ratio in women was associated with a reduction in systolic blood pressure in response to weight loss. While it is possible that selection bias may explain gender differences among programme participants, and smaller numbers of men available for study may obscure associations in men, our data document that even at high levels of obesity, waist-to-hip ratios are associated with hypertension and a clustering of cardiovascular disease risk factors in women. We conclude that body fat distribution, as reflected in waist-to-hip ratios, may be a more robust risk factor in female than in male obese patients and that this risk factor extends to those women with high levels of obesity.