Medical arterial calcification was studied among 4,553 subjects in a 20-year, longitudinal study of Pima Indians. The prevalence and incidence of medial arterial calcification were highest among men, the elderly, and patients with Type 2 (non-insulin-dependent) diabetes mellitus. Medial arterial calcification was most commonly observed in the feet and appeared to progress proximally. Proportional hazards analysis was used to evaluate risk factors for medial arterial calcification in the feet and to evaluate medial arterial calcification as a risk factor for death and for complications of diabetes. Among diabetic patients, risk factors for medial arterial calcification were impaired vibration perception, long duration of diabetes, and high plasma glucose concentration (p less than 0.01 for each). Among nondiabetic subjects, age, male gender (p less than 0.01 for each), and high serum cholesterol concentration (p = 0.02) were risk factors for medial arterial calcification. Nondiabetic subjects with medial arterial calcification did not have higher mortality rates than subjects without medial arterial calcification (rate ratio = 0.95, 95% confidence interval = 0.7-1.3). Diabetic patients with medial arterial calcification, compared with diabetic patients without medial arterial calcification, had 1.5-fold the mortality rate (95% confidence interval = 1.0-2.1), 5.5-fold the rate of amputations (95% confidence interval = 2.1-14.1), 2.4-fold the rate of proteinuria (95% confidence interval = 1.3-4.5), 1.7-fold the rate of retinopathy (95% confidence interval = 0.98-2.8), and 1.6-fold the rate of coronary artery disease (95% confidence interval = 0.48-5.4).