Serum samples from 25 patients at five different stages of syphilis were investigated for their ability to inhibit the adherence of pathogenic Nichols treponemes to cultured human fibroblasts. Serum taken from patients at the end of the primary stage showed an appreciable inhibition of treponemal adherence, and maximum inhibition of adherence was produced by serum from patients with secondary syphilis. Some freshly harvested treponemal suspensions were resistant to the adherence inhibition factors in serum from patients with syphilis; after incubation in vitro for 24 hours this resistance was lost. In vitro incubation almost doubled the number of adherent treponemes/fibroblast. These phenomena are discussed in terms of loss and reconstruction of the treponemal outer envelope. This leads to the suggestion that adherence occurs not only at the tips of the treponemes, but that surface components are also implicated, possibly as an initial contact mechanism. The composition of the outer envelope may in this way determine localisation versus dissemination of the treponemes.