The prevalence of gestational trophoblastic tumors varies widely among different populations: it is lowest in whites (3 to 6/100,000) and highest in Chinese (68 to 202/100,000). This observation suggests that the origin of the disease is different in the two populations. To test this hypothesis, we examined couples in whom the woman developed a gestational trophoblastic tumor in a white population (Pittsburgh) and a Chinese population (Taiwan) for sharing of human leukocyte A, B, DR, and DQ antigens, which we consider markers for sharing of major histocompatibility complex-linked recessive genes affecting both embryogenesis and carcinogenesis. No human leukocyte antigen sharing occurred between partners in Pittsburgh, but there was significant human leukocyte antigen sharing in Taiwan. The latter couples shared human leukocyte antigen B (p less than 0.04) and human leukocyte antigen DQ (p less than 0.007) and shared three or more human leukocyte A, B, DR, and DQ antigens (p less than 0.02) significantly more frequently than did normal couples. However, there was no increased sharing of any specific human leukocyte antigen allele. These findings support the hypothesis that gestational trophoblastic tumors occur on a sporadic basis in whites and on a genetic basis in Chinese.