Tribal communities in India constitute the largest tribal population in the world. There are about 635 biological isolates (tribes and subtribes), which constituted 8.08% (about 84.3 million) of the total population of India as per the 2001 census. Out of 635 scheduled tribes (aborigines), 62 live in the state of Orissa alone forming about 10.8% of the tribal population of India. Orissa state occupies an important place, being the 3rd in rank for the highest concentration of tribal population in the country. In India, tribal communities are highly vulnerable to hereditary diseases and have a high degree of malnutrition, morbidity and mortality. The sickle cell haemoglobinopathy and glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency are important genetic and public health problems in Central-Eastern part of India. In order to map out these genetic disorders among the tribal people, a cross-section of 15 major tribal communities from different parts of Orissa was randomly screened for haemoglobin variants and G6PD deficiency. The high frequency of sickle cell haemoglobinopathy (0-22.4%) and G6PD deficiency (4.3-17.4%), with beta-thalassemia trait (0-8.5%) taking almost an intermediate position, was observed. For G6PD deficiency, hemizygous males as well as female heterozygotes and female homozygotes were detected. Twelve cases showed compound heterozygosity for sickle cell haemoglobinopathy and G6PD deficiency. There seems to be a trend towards an inverse relationship between the sickle cell allele and G6PD deficiency, and sickle cell and beta-thalassemia allele in a cross-section of malaria endemic (Plasmodium falciparum) tribal communities in Orissa. When the frequency of sickle cell allele decreases in a cross-section of malaria endemic tribal population, the frequency of G6PD enzyme deficiency and beta-thalassemia allele increases and vice versa. Natural selection had played a major role in favour of sickle cell, beta-thalassemia and G6PD mutation alleles so that they had probably evolved as a protective mechanism against the lethal effects of malaria in this part of the country. However, the calculated values of 0.074, 0.218 and 0.337, respectively, of Pearson's correlation co-efficient (r), showed no correlation between sickle cell disorders and G6PD deficiency, sickle cell disorders and beta-thalassemia, and G6PD deficiency and beta-thalassemia.