A total of nearly 1,000 persons belonging to a number of caste, religious and tribal groupings in Kerala and the Nilgiri Hills of South India have been tested for genetic variation in 4 blood group, 5 serum protein and 17 enzyme systems as well as haemoglobin. The distribution of blood groups, serum protein and enzyme groups is similar to that reported for other South Indian populations. Abnormal haemoglobins were detected in several populations. Abnormal haemoglobins were detected in several populations, HbS being present in more than 20% of the Irula and Kurumba in the Nilgiri Hills. In the Kerala populations there were 4 examples of Hb AD and 1 of Hb AE. Genetic distance estimates using the gene frequency data indicate that the closest groups are the Nayar and Izhava and the Brahmin and Nayar. The tribal populations are approximately twice as far from the Nayar as they are from the Izhava. The Todas of the Nilgiri Hills are somewhat closer to the Brahmin of Kerala than they are to the other tribal populations.