Legionella pneumophila can invade and grow within explanted alveolar epithelial cells. Given its potential clinical significance, an examination of the molecular basis of epithelial cell infection was initiated. The mip gene encodes a 24-kilodalton surface protein that promotes macrophage infection and virulence. To determine whether this gene is required for pneumocyte infection, we tested a strain bearing a mip null mutation for its ability to infect both explanted type II cells and type I-like cell lines. For infection of type II cells, the infective dose 50% for the Mip-strain was 25-fold higher than an isogenic Mip+ strain. Type I cell monolayers infected with the mutant for 3 days yielded approximately 50-fold fewer bacteria than did monolayers infected with the parental strain. These data indicate that Mip enhances infection of pneumocytes and that L. pneumophila employs some of the same genes (mechanisms) to infect epithelial cells and macrophages.