The erythrocyte sedimentation rate (ESR) was examined annually for 15 years in 1,000 asymptomatic men aged 18-33 years at entry into the study in 1968. The upper limit of the normal (mean + 2 SD) increased from 8 mm in the first hour in persons aged 18 years to 18 mm in those age 45. An increase in the ESR above the age adjusted upper limit of normal on at least three of four consecutive annual examinations was observed in 44 (4.4%) cases. The elevated ESR was associated with a diagnosed disorder in 10 of these 44 cases: myocardial infarctions (four), ankylosing spondylitis (three), inflammatory bowel disease (one), psoriasis (one), and "benign" monoclonal gammopathy (one). A persistently elevated ESR increased the likelihood of disease in general from 3.8% to 22.7% and of myocardial infarction from 0.7% to 9.1%. In eight patients the elevation of the ESR preceded the clinical manifestations by 2-10 years. It is concluded that a persistent moderate elevation in ESR detected in a young adult in the course of screening examinations is a risk factor for the development of disease.