The activity of six intracellular antibiotics, doxycycline, erythromycin, clarithromycin, azithromycin, rifampicin and ciprofloxacin, was tested against 60 strains of Legionella pneumophila (21 of human and 39 of environmental origin). MIC50, MIC90, and MBC values were determined by a microdilution method. Inhibitory and bactericidal activity against human and environmental isolates were similar except for rifampicin, which was 100-fold less active for human strains than for environmental strains, particularly in terms of bactericidal activity. Nevertheless, in general, rifampicin was found to be the most active drug. Among the macrolides tested, clarithromycin showed the greatest activity in MIC assays and erythromycin was the least bactericidal. Azithromycin showed higher MICs and MBCs than the two macrolides, and doxycycline was the least active. The most important factors influencing in-vivo activity of antibiotics are discussed. Even if the in-vitro results cannot be fully extrapolated to activity in vivo, these results indicate the susceptibility of L. pneumophila strains in Italy as a basis for treatment of atypical pneumonia that may be due to Legionella spp.