INTRODUCTION: Influenza-like illness (ILI) and acute respiratory infection (ARI) are common presentations during winter and indiscriminate antibiotic use contributes significantly to the emerging post-antibiotic era. METHODOLOGY: Otherwise healthy 152 patients, presenting to outpatient clinics with ILI/ARI, were included. Patients had history & physical, CRP, hemogram and nasopharyngeal swabs for rhinovirus A/B, influenza A/B, adenovirus A/B/C/D/E, coronavirus 229E/NL63 and OC43, parainfluenza virus 1/2/3, respiratory syncytial virusA/B, metapneumovirus and Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila and Bordetella pertussis by PCR and for ABHS culture. RESULTS: Median (IR) age was 26.5 (16.5). Time to presentation was shorter in men (p = 0.027). Patients with rhinovirus had lower rates (20%) of myalgia (p = 0.043). Patients with influenza virus had higher rates (97%) of elevated CRP (p = 0.016). Logistic regression revealed that patients with ILI/ARI and CRP >/= 5 mg/L were 60 times more likely to have influenza virus infection than other viral agents (OR = 60.0, 95% CI = 2.65 to 1,358.2, p = 0.010). Rhinovirus predominated in December (54%), March (36%), and April (33%). Influenza virus predominated in January (51%). Fever was most common with adenovirus (p = 0.198). All GABHS cultures were negative. Atypical organisms and Bordetella pertussis were negative in all but one patient. CONCLUSIONS: Influenza virus is the most likely pathogen in ILI/ARI when CRP >/= 5 mg/L. This might be explained by tissue destruction. Myalgia is rare with rhinovirus probably due to absence of viremia. Negative bacteria by PCR and culture suggest unnecessary antibiotic use in ILI/ARI.