Legionella pneumophila is a protozoan parasite that causes Legionnaires' disease. Its ability to do so is dependent on its capacity to replicate intracellularly within a phagosome that is not trafficked through the endosomal-lysosomal pathway and is surrounded by the rough endoplasmic reticulum. Within this unique niche, the bacterium undergoes alterations in gene expression. In addition, many virulence-related phenotypes that are induced in vitro by starvation are expressed intracellularly as the bacteria exit the logarithmic growth phase. (p)ppGpp appears to signal expression of the virulence-related genes in L. pneumophila upon starvation. This growth phase-dependent phenotypical transition is concomitant with lysis of the host cell, in which both necrosis and apoptosis seem to play roles. Many genetic loci that are required for intracellular replication within mammalian and protozoan cells have been identified, and the majority of them are novel. Two secretion systems have been identified, one of which may be distantly related to type IV secretion systems. The other is a type II secretion system similar to the PilBCD piliation system of Pseudomonas aeruginosa.