Mortality rates of coronary heart disease are much lower in Japan than in the United States. The authors' previous report on coagulation factors showed that population levels of plasma fibrinogen and factor VII activity parallel this mortality difference. To investigate other hemostatic variables, the authors assessed indicators of fibrinolytic activity (tissue plasminogen activator antigen) and coagulation inhibition (antithrombin III activity and protein C) in 136 men aged 34-55 years in four different samples: rural Japanese, urban Japanese, Japanese Americans, and Caucasian Americans. Mean tissue plasminogen activator antigen was higher in Caucasians and Japanese Americans than in rural and urban Japanese (p less than 0.01), while a contrasting trend in mean antithrombin III activity was suggested (p = 0.10). No significant differences were observed in mean levels of protein C. After controlling for known coronary risk factors, mean levels of tissue plasminogen activator antigen remained significantly different across the four samples (p less than 0.01); mean antithrombin III activity was not different (p = 0.23). Population differences in tissue plasminogen activator antigen parallel the coronary heart disease mortality difference between Japan and the United States. Although no definite evidence is available showing that tissue plasminogen activator antigen is a risk factor for coronary heart disease, the present study suggests a positive ecologic association between this hemostatic factor and coronary heart disease mortality.