The presence of several polymorphic markers along the alpha-globin gene complex allows the identification of haplotypes associated with alpha-thalassemia determinants. These are found at very high frequencies in geographic areas where malaria is or has been endemic which suggests a positive selective role by the parasitic disease in favour of alpha(+)-thalassemia mutants. A population survey among forest tribal communities from Andhra Pradesh, India, revealed the prevalence and molecular heterogeneity of alpha(+)-thalassemia determinants presumably due to a long backdated malaria endemicity among these populations. Analysis of the tribal alpha-thalassemia haplotypes has shown a great degree of genetic heterogeneity which can be explained as the result of multiple recombination events in the presence of natural selection by malaria.