We investigated an hypothesis relating the Duffy-negative blood type with insusceptibility to vivax malaria—and previously associated only with people of West African ancestry—in three population samples of eastern African stock. The samples included Nilotic and Hamitic-Semitic residents of a malarious locale in Ethiopia and Hamito-Semites in Addis Ababa where malaria is not endemic. Fresh red blood cells from 191 subjects were tested with Duffy antisera, anti-Fya and anti-Fyb. Duffy-positive rates in the malarious community were 8% for the Nilotes and 70% for the Hamito-Semites; the Hamito-Semites in Addis Ababa were 98% Duffy-positive. The relative prevalences of Plasmodium vivax in the two study groups at risk to malaria were 2.4% for the Nilotes and 27.3% for the Hamito-Semites, producing a ratio similar to the ratio of Duffy-positives in the two samples. We interpret the data as supportive of the Duffy-vivax hypothesis with reference to a part of eastern Africa, and we suggest that the Duffy-negative genotype may represent the original, rather than the mutant, condition in tropical Africa.