Abstract In Uppsala, extensive epidemiological and clinical studies on insulin resistance and diabetes have been ongoing for the past 30 years. A prospective cohort study of men born 1920-24, living in Uppsala County, was initiated during 1969-74 (the Uppsala Longitudinal Study of Adult Men, ULSAM). Risk factors for cardiovascular disease were examined in 2,322 men, and re-examinations have been performed every 10 years. At the first follow-up, when the men were 60 years old, insulin resistance was found to be a risk factor for development of hypertension and diabetes. In addition, treatment with antihypertensive medication was an independent risk factor for development of diabetes. These findings resulted in a series of clinical studies on metabolic effects of antihypertensive agents. At the second follow-up, when the men were 70 years old, the development of hypertension and diabetes was once again in focus, but at this time, cross-sectional and prospective studies of other cardiovascular determinants, such as circadian blood pressure pattern, left ventricular geometry and function, muscle morphology, ion status, fibrinolysis and cognitive function, were also performed. The cohort has furthermore been linked to the Swedish census and hospital discharge and cause of death registries, it has been used for studies on relationships between birth weight and cardiovascular disease, and genetic analyses have been performed, taking advantage of the long observation time obtained in this cohort. The cohort is currently being re-examined for the third time, and will hopefully continue to provide valuable information on the epidemiology of diabetes and cardiovascular disease in the future.