Diseases caused by Chlamydia are based on intense and chronic inflammation elicited and maintained by reinfection or persistent infection. The traditional view in the field is that disease is mediated by antigen-dependent delayed-type hypersensitivity or autoimmunity. This immunological paradigm has served as the basis for years of chlamydial research but the mechanism or the antigen that causes pathology has yet to be unequivocally revealed. Recent research on responses elicited in Chlamydia-infected cells defines a new direction for our understanding of this microorganism-host interaction and provides the basis for a reassessment of disease mechanisms. Chlamydia-infected non-immune mammalian cells produce proinflammatory chemokines, cytokines, growth factors and other cellular modulators. This cellular response to infection supports an alternative hypothesis for chlamydial pathogenesis: the inflammatory processes of chlamydial pathogenesis are elicited by infected host cells and are necessary and sufficient to account for chronic and intense inflammation and the promotion of cellular proliferation, tissue remodeling and scarring, the ultimate cause of disease sequelae.