A close relationship between the four human treponematoses is suggested by their clinical and epidemiological characteristics and by such limited knowledge of the treponemes as there is at present. No treponeme of this group (except for that of the rabbit) is known other than in man, but the human treponemes probably arose long ago from an animal infection. The long period of infectiousness of pinta suggests that it may have been the earliest human treponematosis. It may have been spread throughout the world by about 15 000 B.C., being subsequently isolated in the Americas when the Bering Strait was flooded. About 10 000 B.C. in the Afro-Asian land mass environmental conditions might have favoured treponeme mutants leading to yaws; from these, about 7000 B.C., endemic syphilis perhaps developed, to give rise to venereal syphilis about 3000 B.C. in south-west Asia as big cities developed there. Towards the end of the fifteenth century A.D. a further mutation may have resulted in a more severe venereal syphilis in Europe which, with European exploration and geographical expansion, was subsequently carried throughout the then treponemally uncommitted world. These suggestions find some tentative support in climatic changes which might have influenced the selection of those treponemes which still survive in humid or arid climates. Venereal transmission would presumably remove the treponeme from the direct influence of climate. The author makes a plea for further investigation of many aspects of this subject while this is still possible.