Coronary heart disease (CHD) is rare in Japanese subjects and serum cholesterol levels are low. However, no data have been published relating the effect of serum cholesterol levels to the incidence of acute myocardial infarction (AMI) in Japan. Data from a large community-based mass screening registry are available for the geographically isolated island of Okinawa, Japan (1980 census, 1.11 million). A total of 38,053 participants (17,859 men and 20,194 women) whose serum cholesterol levels were determined in the 1983 mass screening were examined to determine whether they had experienced AMI. Every case of AMI that occurred during a 3-year period (1 April 1988 to March 1991) throughout Okinawa was recorded in a separate registry. The total number of cases of AMI was 1,021 (674 men and 347 women). Of these, 65 patients (41 men and 24 women) were identified by name, sex, birth date, and zip code in the mass screening registry. The cumulative incidence of AMI increased with the serum level of cholesterol: 42.1 (serum cholesterol ≤ 167 mg/dl), 133.5 (serum cholesterol 168-191 mg/dl), 188.9 (serum cholesterol 192-217 mg/dl), and 323.0 (serum cholesterol ≥ 218 mg/dl) per 100,000 screened subjects. Multiple logistic analysis was conducted to examine the effect of serum cholesterol on the risk of AMI with adjustment for other variables such as sex, age, systolic and diastolic blood pressure, and proteinuria. The adjusted odds ratio (95% confidence interval) of the observed serum levels of cholesterol was 1.66 (1.29-2.15) with a reference serum cholesterol level of ≤ 167 mg/dl. The risk of AMI increased in proportion to the serum level of cholesterol. Serum cholesterol is an independent predictor of AMI in Okinawa, Japan. (Jpn Circ J 1998; 62: 7 - 14)