Microbiologic studies (MBSs) fail to identify a specific pathogen in more than 50% of patients with community-acquired pneumonia (CAP). The 1993 American Thoracic Society guideline (ATS-GL) for the management of CAP advised selecting initial antibiotic regimens based on severity of illness and comorbidities. Our study evaluated the role of initial MBS in adult patients hospitalized with CAP and treated according to the ATS-GL. In 184 patients hospitalized at our facility for CAP in 1996, and treated according to the ATS-GL, 25 (14%) failed to respond to initial antibiotic regimens. In these nonresponders, there was no difference in mortality between those in whom antibiotics were changed empirically, and those with MBS-guided changes. We conclude that initial MBS may not be warranted in many adult patients admitted for CAP. Exceptions include patients with conditions that predispose to less common, more resistant pathogens.