Type-4 pilus-mediated adherence of Neisseria gonorrhoeae and Neisseria meningitidis is considered to be a crucial early event in neisserial infections. In addition to the principal pilus subunit (pilin or PilE), both pathogens produce low quantities of a phase-variable PilC protein which is implicated in pilus biogenesis and pilus-mediated epithelial cell adherence. The identity, however, of the pilus adhesin has remained obscure. Here we describe the isolation of a PilC protein from a gonococcal overproducing strain and demonstrate its specific interaction with human epithelial cells. Our results are consistent with the cell and species tropisms of neisserial infections. Binding of PilC effectively competes with pilus-mediated, but not Opa-mediated, attachment of N. gonorrhoeae and of N. meningitidis, indicating that both pathogens interact with identical or very similar epithelial cell receptors. Immunogold electron microscopy using antisera raised against purified PilC and synthetic peptides locates PilC at the tip of gonococcal pili. PilC thus represents an essential pilus-associated adhesin, providing a rationale for selective protection against neisserial infections.