The adherence of Chlamydia trachomatis LGV440(Ll) to human HeLa 229 and mouse McCoy cells was stimulated by the lectin wheat germ agglutinin (WGA) and inhibited by the sugars Nacetyl-D-glucosamine, N-acetyl-D-galactosamine and chitobiose, but only when the chlamydiae had been passaged several times in HeLa cells. After passage in McCoy cells, the lectin and the sugars elicited little response. The non-LGV serovar UW-3 1 (K), however, differed from LGV440(L1) in that, regardless of passage, the lectin and sugar effects were observed only in HeLa cells. Affinity chromatography on W GA-agarose confirmed that HeLa-grown LGV-44O(L1) bound to a significantly greater extent relative to McCoy-grown chlamydiae. In addition, participation of heterogeneous chlamydia1 ligands was suggested by the observation that the adherence of heated (60 "C, 5 min) UW-3l(K) to HeLa cells at 37 "C was not inhibited at all, but at 5 "C, the adherence rate was greatly reduced, indicating the participation of heatstable as well as heat-labile ligands. These data are interpreted to indicate that the passage history of C. trachomatis results in the acquisition of altered surface components that participate in the initial interaction of the bacterium with the host.