Although empiric antibiotic therapy is often used for sinusitis, the emergence of antibiotic resistance has increased the failure rate of this approach. Culture-directed therapy usually increases treatment success, but traditional antral puncture is often accompanied by poor patient and physician acceptance. Endoscopically directed middle meatal aspiration culture is increasingly used in this setting, but studies have not convincingly demonstrated the validity of this technique. Both endoscopic middle meatal and direct antral cultures were performed during endoscopic sinus surgery. Cytologic examination was performed to confirm the presence of inflammatory cells. When culture results were compared in 21 specimen pairs, exact correlation was found in 18 (85.7%). Based on this study, endoscopically directed middle meatus aspiration culture appears to be a valuable alternative to antral puncture for guiding organism-specific antibiotic therapy in sinusitis.