The clinical features and histopathologic changes in 20 cases of luetic lymphadenitis are analyzed. Nine of the 20 patients complained of a mass and pain in the inguinal region. In six patients surgical procedures were performed because the possibility of incarcerated hernia could not be excluded. Malignant disease was considered in the clinical differential diagnoses of four of seven patients who had generalized enlargement of their lymph nodes. Syphilis was diagnosed preoperatively in three cases. The histologic changes of luetic lymphadenitis are variable. Those which occurred most frequently in the inguinal lymph nodes were chronic inflammation and extensive fibrosis of the capsule and pericapsular tissues, numerous plasma cells, vascular changes and follicular hyperplasia. Although this constellation is not pathognomonic of luetic lymphadenitis, the changes are sufficiently distinctive that syphilis should be considered a diagnostic possibility. Spirochetes were identified in the lymph nodes of all patients in the study. In each of two cases a histologic diagnosis of sarcoidosis was considered because the lymph nodes contained noncaseating granulomas. Other tissue reactions in the inguinal lymph nodes included abscesses that contained spirochetes and granulomas associated with giant cells. Follicular hyperplasia was present in lymph nodes from the occipital, cervical, and axillary regions. Spirochetes were sought and identified in these nodes because these patients’ serologic tests for syphilis had been positive. Although spirochetes were found in all portions of the lymph nodes, they were most consistently identified in the walls of blood vessels.