A minority of patients with upper respiratory tract infections (URTI) have a bacterial infection and may benefit from antibiotherapy. In previous investigations we showed that in patients suffering from acute rhinosinusitis associated with the presence of Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis in their nasopharygeal secretions, resolution of symptoms was significantly improved by antibiotic treatment. The present analysis was performed to determine whether specific clinical symptoms or signs observed during careful endoscopic examination of the nasal cavities could help the clinician to identify a subset of patients with moderate forms of acute rhinosinusitis infected with pathogenic bacteria. Detailed clinical histories were obtained and medical examinations performed in 265 patients (138 females, 127 males; mean age 35 years) presenting with a < 4-week history of URTI symptoms but who did not require immediate antibiotic therapy for severe rhinosinusitis. The presence of three pathogenic bacteria (S. pneumoniae, H. influenzae and M. catarrhalis) was determined in all patients by culture of nasopharyngeal secretions. Azithromycin (500 mg/day for 3 days; n = 133) or placebo (n = 132) were randomly given to all patients in a double-blind manner. Pathogenic bacteria were found in 77 patients (29%). The clinical signs and symptoms significantly associated in a multivariate model with the presence of bacteria included colored nasal discharge (p < 0.003), facial pain (p < 0.032) and radiologically determined maxillary sinusitis (complete opacity, air-fluid level or mucosal thickening > 10 mm) (p < 0.001). This best predictive model had a sensitivity of 69% and a specificity of 64% and therefore could not be used either as a screening tool or as a diagnostic criterion for bacterial rhinosinusitis. In the group of patients with positive bacterial cultures, resolution of symptoms at Day 7 was observed in 73% of patients treated with azithromycin and in 47% of patients in the placebo group (p < 0.007). We conclude that signs and symptoms of acute rhinosinusitis in patients with mild-to-moderate clinical presentations are poor predictors of the presence of bacteria.