The action of chemicals such as calcium hydroxide (Ca(OH) 2 ) and sodium hypochlorite (NaOCI) that are used as tissue solvents may be enhanced by prolonged contact. The objective of this study was to determine if sealing Ca(OH) 2 and NaOCI into the canal space would improve debridement of both the main canal and areas inaccessible to files. Mesial root canals of 75 freshly extracted mandibular molars were step-back hand-instrumented. Another six molars were controls. Either Ca(OH) 2 , NaOCI, or no medication was sealed in the canals for 1 or 7 days. Canals were finally irrigated with H 2 O and prepared for histological evaluation. The cleanliness of main canals and inaccessible areas (isthmi and fins) at the apical, middle, and coronal thirds was examined, scored, and compared by nonparametric statistical analysis. Results showed no significant differences among different groups in either the 1-day or 7-day time intervals in either the main canal or inaccessible areas. Instrumentation combined with NaOCI irrigation alone accounted for the removal of tissue in the main canal. In conclusion, in this system, prolonged contact with Ca(OH) 2 and NaOCI was similarly ineffective; neither contributed significantly to canal debridement.