The literature on the genetic regulation of susceptibility in leprosy, tuberculosis, amd leishmaniasis is critically reviewed. Of the three groups of diseases, leprosy has received the most attention from the standpoint of human genetics. There is now evidence that genetic factors, some of them HLA-linked, play a role in tuberculoid leprosy. However, the evidence leaves considerable room for environmental determinants in addition to genetic background. Several twin studies of tuberculosis have favored some genetic factors in clinical tuberculosis, but their evidence is mitigated by the many biases underlying such studies. Though very little work has been done on the genetics of leishmaniasis in man, experimental studies in mice have begun to unravel mechanisms controlling successive steps in the course of both L. donovani and L. torpica infections. It is suggested that future work should concentrate on moving from genetics to biochemical genetics in the mouse, should extend family studies in conjunction with markers in man, and should place high priority on confirmation of reported leprosy type discordance among monozygous twins.