C. pneumoniae has excited considerable attention during the last decade, not only as a respiratory pathogen but because of its association with a number of acute and chronic diseases, including atherosclerosis. The true linkage and causality of C. pneumoniae infection in the development of chronic manifestations remain puzzling. Efficient activation of type 1 T cell responses and secretion of IFN- γ mediates immune defense and provides improved recovery from reinfection. However, the factors that expose some individuals to impaired clearance of Chlamydia or drive immune responses to pathogenic ones are not known. The role of host genetic background, HLA molecules and cytokine gene polymorphism, environmental and epidemiological factors, mixed infections, and species or dose of the infecting agent probably all interact in a final balance of the immune defense mechanisms. A better understanding of the immunoregulatory processes during chlamydial infections in humans is necessary to furnish a novel immunotherapeutic strategy for treatment of acute C. pneumoniae infection and thereby to prevent development of disease manifestations that are associated with chronic or repeated infections. The understanding is facilitated by answering to the question whether the susceptibility for repeated infections is due to impaired type 1 response or activation of type 2 responses. The impact of primary host cells into developing immunity is a question of major importance and should be studied in humans.