OBJECTIVE: Incorrect and unnecessary antibiotic prescribing enhancing bacterial resistance rates might be reduced if viral and bacterial lower respiratory tract infections (LRTI) could be differentiated clinically. Whether this is possible is often doubted but has rarely been studied in general practice. STUDY DESIGN AND SETTING: This was an observational cohort study in 15 general practice surgeries in the Netherlands. RESULTS: Etiologic diagnoses were obtained in 112 of 234 patients with complete data (48%). Viral pathogens were found as often as bacterial pathogens. Haemophilus (para-) influenzae was most frequently found. None of the symptoms and signs correlated statistically significantly with viral or bacterial LRTI. Erythrocyte sedimentation rate >50 (odds ratio [OR] 2.3-3.3) and C-reactive protein (CRP) >20 (OR 2.1-4.6) were independent predictors for viral LRTI and bacterial LRTI when compared with microbiologically unexplained LRTI. CONCLUSION: Extensive history-taking and physical examination did not provide items that predict viral or bacterial LRTI in adult patients in daily general practice. We could not confirm CRP to differentiate between viral and bacterial LRTI.