To study the epidemiology of human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan, we conducted two nationwide surveys between October 1986 and March 1989. A total of 710 patients with HAM (definite HAM, 589; probable HAM, 121) were reported. Of the 589 patients with definite HAM, 69% were residents of the areas with the highest prevalence HTLV-I in Japan. To determine the importance of blood transfusion in the pathogenesis of HAM/TSP, we performed a case-control study in the Kagoshima district in southern Japan. Significantly more patients with HAM reported a history of blood transfusion (26/129, or 20%) than did subjects in a health survey of the general population (41/1,290, or 3%; odds ratio = 7.7, p less than 0.001) or than did hospitalized neurological patients (6/119, or 5%; odds ratio = 4.8, p less than 0.001). Furthermore, the cumulative percentages of the intervals between blood transfusion and the onset of the symptoms of HAM fit a lognormal curve, suggesting that transfusion was an important common exposure. Blood transfusion probably transmitted HTLV-I to the patients with transfusion-associated HAM because there was a significant decrease in the number of patients with the transfusion-associated HAM who received blood after implementation of nationwide screening of blood donors in 1986 (p = 0.004). In the first 2 years, screening the blood supply in Japan appears to have decreased the number of reported patients with HAM by 16%.