Restriction endonuclease analysis was used to test a proposed genetic model using alpha-globin gene number to account for the observed distributions of the proportions of hemoglobin (Hb) S in sickle cell trait. In a subsample of specimens collected during a population survey in India, these studies confirmed that the postulated genotype was present in 22 of the 23 individuals examined. In the study population, the number of alpha-globin genes explains about 90% of the variance in the proportion of HbS in sickle cell trait (r2 = 0.895, p less than 10(-10)).