Takayasu's disease is characterized by a "pulseless" condition which most often occurs in young females from Asian or South American areas. The cause of this disease remains obscure. Recently, we encountered monozygotic, Japanese, identical twin sisters, both of whom were diagnosed as having Takayasu's disease. The parents, two sisters, and one brother are healthy. HL-A typing analyses revealed that one haplotype found in the father had passed only to these twins. Such observations led us to search HL-A typing in Takayasu's disease to determine the possible participation of genetic factors in the pathogenesis of this morbid condition. Ten families, including that of our own patient, have been reported in the literature in Japan, as family cases of Takayasu's disease. HL-A typings in A and B locus analyzed in all family members of six families in attempts to find a common haplotype composed of A9, A10, B5, or BW40 in patients with Takayasu's disease, were confirmed statistically (chi 2 = 7.8, 0.01 less than p less than 0.05). In a population study, HL-A typing analyses of 65 patients with Takayasu's disease also revealed a high frequency of HL-A A10 and HL-A B5 with the level of 15.3 and 17.0 in the chi 2-test (p less than 10(-4)), as compared with the frequency in 128 healthy Japanese. These data strongly suggest that a genetic-related factor has to be given serious consideration.