In order to determine the causes of treatment failure in community-acquired pneumonia (CAP) clinical trials, a MEDLINE search for all CAP studies published between 1990 and 1997 was performed. Prospective, randomized studies comparing the efficacy of two or more antibiotics in CAP were selected. Treatment failure was defined as persistent fever, deterioration of patient's condition, or a change in the prescribed antibiotic regimen. In 16% of the cases included in the clinical trials, the treatment of CAP is unsuccessful. A significant number of identified failure cases were owing to antibiotic side-effects. Resistant pathogens are an unusual cause of failure whatever the antibiotic used.