Legionellae are important etiological agents of pneumonia. Legionella pneumophila (predominantly serogroup 1) is detected in most cases of legionellosis; other species only occasionally cause infections, predominantly in immunocompromized patients. Aquiferous technical systems are the primary source of infection (air-conditioning systems, refrigerators, showers, whirlpools, springs, taps, moisturizing equipment, medical nebulizers, and swimming pools). Legionellae are present in the water in these systems, within the amoebae, flagellates, and ciliates in which they replicate. After inhalation of contaminated aerosols, the bacteria multiply intracellularly within alveolar macrophages. The ability to multiply within monocytic host cells is usually considered to correspond to pathogenicity. The mechanisms of intracellular replication have been only partially characterized. Analysis of the molecular pathogenesis of Legionella infection, both in the pathogen itself and in the host cell, is the subject of current research and may lead to new options in prophylaxis and treatment. We have established the human Mono Mac 6 cell line (MM6) instead of the previously used histiocytic lymphoma cell line U 937 or the promyelocytic leukemia cell line HL-60 to investigate the intracellular replication of legionellae and the molecular pathogenesis of Legionella infection within human monocytic host cells. MM6 cells represent a more mature macrophage-like cell line that expresses phenotypic and functional properties of mature monocytes and that does not need to be stimulated by phorbol esters or 1,25-dihydroxyvitamin D3. A good correlation between the prevalence of a given Legionella species and its intracellular multiplication in MM6 cells could be demonstrated.In addition to Legionella, MM6 cells were found to support the intracellular growth of Mycobacterium tuberculosis and Chlamydia pneumoniae, two other important bacterial agents involved in induction of pneumonia. Therefore, the MM6 model might be adaptable to investigations of the molecular pathogenesis of other intracellular bacteria that can replicate within human monocytes and induce disease.