Successful treatment of influenza depends on accurate diagnosis of illness and prompt intervention. However, there is a lack of data comparing clinical and laboratory diagnostic techniques. In this study, clinical diagnosis of community cases of influenza is compared with classical laboratory techniques used for diagnosis of influenza such as virus culture, paired hemagglutination inhibition serology, and newer molecular diagnostic methods (eg, multiplex reverse transcription polymerase chain reaction). A range of clinical symptoms were scored for severity, and correlation of symptom scores with laboratory diagnosis was evaluated. Total symptom scores at baseline showed a significant association toward greater severity with increasing number of positive test results (P<.001). Increasing number of positive test results also showed a significant correlation with a longer time to alleviation of symptoms of influenza (P = .001). The authors suggest that reverse transcription polymerase chain reaction be considered a gold standard for detection of influenza when presentation occurs within the first 48 hours of illness, concluding that when influenza was circulating and clinical diagnostic criteria were applied, diagnosis of influenza was accurate in more than 70% of adults on clinical grounds alone. This highlights the need for primary care physicians to be alerted to circulating influenza and to be aware that presentation with cough and fever are the most predictive symptoms.