A variety of treponemal diseases other than syphilis occur endemically in many tropical areas of the world. They are distinguished from disease caused by T pallidum by their nonsexual transmission via direct skin contact, their relatively high incidence in certain geographic areas and among children, and their tendency to produce less severe visceral manifestations. As in syphilis, skin, soft tissue, and bone lesions may develop, organisms can be demonstrated in infectious lesions with darkfield microscopy or immunofluorescence, but cannot be cultured in artificial media; the serologic tests for syphilis are positive; molecular methods such as PCR and genome sequencing are available, but not widely used in endemic areas; the diseases have primary, secondary, and sometimes tertiary stages. There is evidence that infection with these agents may provide partial resistance to syphilis and vice versa. Treatment with 2.4 million units of benzathine penicillin G intramuscularly is generally curative in any stage of the non–sexually transmitted treponematoses. In cases of penicillin hypersensitivity, tetracycline, 500 mg orally four times a day for 10–14 days, is usually the recommended alternative. In randomized controlled trials, oral azithromycin (30 mg/kg once) was noninferior to benzathine penicillin G for the treatment of yaws in children.