The histological appearances found in biopsies from fifty-seven patients with secondary syphilis have been correlated with the clinical morphology of the eruptions. Considerable variation of histological pattern was encountered, and the frequency with which some of the classically described changes were found to be absent or inconspicuous is stressed. Of particular interest were the findings that, in nearly one-quarter of the biopsies, plasma cell infiltration was either absent or very sparse, and that vascular damage was seen in less than half. Where present, the vessel changes were almost entirely confined to swelling of the endothelial cells. Proliferation of the endothelial cells was most uncommon. The epidermis was very frequently involved in the inflammatory process. Exocytosis, spongiosis, parakeratosis, and acanthosis were the most frequent changes. No consistent histological difference between papular and papulo-squamous lesions could be found but macular lesions demonstrated more superficial and less intense dermal infiltration as well as less severe epidermal involvement. In late secondary lesions, the infiltrate became granulomatous, but in other respects the duration of the exanthem could not be correlated with the pathology. The differential diagnosis from pityriasis lichenoides and other inflammatory dermatoses is discussed and the value of histopathology in the diagnosis of secondary syphilis is emphasized.