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The purpose of the present study was to determine if exposure to intracanal calcium hydroxide [Ca(OH2)] alters the fracture resistance of human root dentin. One hundred and two freshly extracted single rooted human teeth divided into three groups of 34 teeth each. Coronal access and endodontic instrumentation using round burs, stainless steel files, and Profile GT rotary files were completed for each tooth. The prepared root canal system of each tooth was filled with saline solution (group 1), USP Ca(OH)2 (group 2), or Metapaste (group 3). The apicies and access openings were sealed with composite resin and the teeth were immersed in saline. After 30 days, the roots of 17 teeth from each group were sectioned horizontally into 1-mm thick disks and each disk was loaded to fracture at 2.5 mm/min with a SATEC universal-testing machine. After 180 days the same procedure was performed on the remaining 17 teeth in each of the 3 groups. The peak load at fracture was measured for each dentin disk. Data were analyzed using one-way ANOVA and a post hoc Student-Newman-Keuls test. After 30 days exposure to the test solution, there was no difference in the peak load at fracture for the three groups of teeth. However, after 180 days, the roots of the teeth exposed to USP Ca(OH)2 showed a significant decrease in peak load at fracture when compared to the 30-day groups and the 180-day groups exposed to saline or Metapaste.