The likely efficacy of four antibiotics of possible use in the treatment of Legionnaires' disease was assessed in terms of their capacity to inhibit the replication of Legionella pneumophila within guinea-pig alveolar macrophages and polymorphonuclear leukocytes (PMN) compared with their minimum inhibitory concentrations (MIC) in vitro. All the antibiotics used had similar MIC values with regard to L. pneumophila (0.032-0.062 mg/l), but differences of up to 100 fold in the concentration required to eliminate viable intracellular organisms were observed. The most effective antibiotics were found to be rifampicin and ciprofloxacin. These eliminated viable L. pneumophila from alveolar macrophages and PMN at concentrations of 0.005 and 0.01 mg/l respectively, whereas erythromycin and gentamicin required higher concentrations of 0.1 and 0.5 mg/l respectively. It is suggested that assays performed in cultures of relevant cells may provide useful additional means of assessing antibiotic efficacy against intracellular pathogens and help to explain discrepancies otherwise observed between in vitro and in vivo findings.