This study intended to examine histologically root canal-treated teeth evincing apical periodontitis lesions and correlate the findings with clinical observations. Specimens were obtained from 24 patients (12 asymptomatic and 12 symptomatic) by extraction or endodontic surgery and consisted of roots or root tips and the associated pathologic lesion. Specimens were processed for histologic analysis, and serial sections were evaluated. Findings were correlated with clinical observations according to the presence or absence of symptoms. The mean period elapsed from treatment to specimen retrieval in the asymptomatic group was 7.5 years, as compared with 2.2 years in the symptomatic group. All specimens exhibited periradicular inflammation. Bacteria were visualized in all cases, except for 1 specimen from the asymptomatic group in which a foreign body reaction to overfilled material was the probable reason for emergent disease in a previously vital case. Irrespective of the presence of symptoms, bacteria were always located within the root canal system, although they were also observed in the periradicular tissues in 1 asymptomatic and 4 symptomatic teeth. In general, intraradicular bacterial colonization was heavier in symptomatic failed teeth. The present findings support the role of intraradicular infections, usually in the form of biofilms, as the primary cause of endodontic treatment failure.