The prevalence of peripheral arterial disease is known to be higher in subjects with diabetes mellitus or impaired glucose tolerance compared with non-diabetic subjects. The objective of study 1 was to determine whether this could be explained by differing levels of 'traditional' risk factors, such as smoking, hypertension, dyslipidaemia and obesity. Methods: 1,592 men and women aged 55-74 years were selected at random from the age-sex registers of 11 general practices throughout Edinburgh, Scotland. Subjects underwent a comprehensive medical examination, including assessment for peripheral arterial disease (positive intermittent claudication questionnaire or major asymptomatic disease on non-invasive testing), a glucose tolerance test and measurement of cardiovascular risk factors (including smoking, blood pressure, body mass index and serum lipids and lipoproteins). Results: 288 subjects (18.7%) were found to have diabetes or impaired glucose tolerance (IGT). The prevalence of peripheral arterial disease was greater in subjects with diabetes or IGT (20.6%) compared to those with normal glucose tolerance (12.5%) (age and sex adjusted OR 1.45; 95% CI 1.03, 2.04). In subjects with diabetes or IGT, mean levels of smoking, systolic blood pressure and serum triglycerides were significantly higher in subjects with peripheral arterial disease than in those without disease (p£0.05). In general, levels of cardiovascular risk factors were higher in subjects with diabetes or IGT compared with normal glucose tolerant subjects; this included systolic blood pressure and triglycerides, but not smoking. In multivariate analysis, subjects with diabetes or IGT no longer had a significantly higher risk of peripheral arterial disease after adjusting separately for systolic blood pressure (OR 1.22, 95% CI 0.85, 1.73) or serum triglycerides (OR 1.26 95% CI 0.89, 1.79). Simultaneous adjustment for both risk factors reduced the odds of disease further to 1.11 (95% CI 0.78, 1.58). Conclusions: Raised levels of serum triglycerides and systolic blood pressure in subjects with diabetes or IGT may explain a major portion of their increased risk of peripheral arterial disease. The objectives of study 2 were to determine whether, in non-diabetic men and women from the general population, there was an association between peripheral arterial disease and (i) plasma insulin levels or (ii) endogenous steroid sex hormones.