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HL-A antigens were determined for the A and B loci among 164 Chamorros living on Guam, Rota, and Saipan in the southern Mariana Islands of Micronesia. The overall antigen phenotype and gene frequencies for the Chamorro population are presented. Comparisons were made between Chamorros and other Pacific populations using HL-A antigen phenotype frequency distributions and analysis of genetic distance. Results agree with historical accounts of admixture between Chamorros and Filipinos during the Spanish colonial era, and data from blood group studies which show close similarities between these populations. The disease, amyotrophic lateral sclerosis, in very high frequency among Chamorros, also exhibits high local prevalences in Japanese and Filipinos, who are in closest proximity to the Chamorros by genetic distance analysis.