The Comorian population is historically considered a blend of influences from African Bantus, Arabs, and possibly Austronesians. In this study we present the first genetic data on the current Comorian population. Serologic analysis of the six major blood group systems (ABO, RH, KEL, FY, JK, and MNS) was performed on 164 individuals from Grande Comore Island (Njazidja). In addition, Duffy genotypes were determined by polymerase chain reaction using allele-specific primers. Our findings establish a high frequency of the Fy(a- b-) phenotype (86%), presenting the same genetic background as in sub-Saharan Africa. Analysis of genetic frequencies, distances, and admixture with other populations indicates that African Bantus made the main contribution to the gene pool (73.2%+/-15.5%). The Arab contribution from the Arabian peninsula was smaller (24.2%+/-7%) and the Indonesian contribution was minor (2.6%+/-9%). The major Bantu contribution was commensurate with the Bantu cultural influence. The contribution from the Arabian peninsula seemed in relation to its permeating religious and linguistic influence. As with the language, the Indonesian contribution to the Comorian gene pool was small. These results are in agreement with historical, sociological, and linguistic data.