The evidence for a genetic determination of susceptibility to leprosy is reviewed. To test the hypothesis that an HLA (histocompatibility leukocyte antigen)-linked gene is associated with such susceptibility, the association between the distribution of leprosy within a family and the segregation of HLA haplotypes was investigated among 72 families who lived in Karigiri, Tamil Nadu State, South India. A statistically significant association was found for families in which siblings had tuberculoid leprosy and in which neither parent had leprosy. The findings from the data of this study agree with those of two previous studies carried out among smaller populations is Surinam and Wardha, Maharashtra State, India. Such an agreement suggests that a genetic determinant which is linked to the major HLA locus on chromosome 6 and which is probably recessive affects susceptibility to tuberculoid leprosy in humans.