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This study determined if any of six endodontic solutions would have a softening effect on resorcinol-formalin paste in extracted teeth, and if there were any differences in the solvent action between these solutions. Forty-nine single-rooted extracted teeth were decoronated 2 mm coronal to the CEJ, and the roots sectioned apically to a standard length of 15 mm. Canals were prepared to a 12 mm WL and a uniform size with a #7 Parapost drill. Teeth were then mounted in a cylinder ring with acrylic. The resorcinol-formalin mixture was placed into the canals and was allowed to set for 60 days in a humidor. The solutions tested were 0.9% sodium chloride, 5.25% sodium hypochlorite, chloroform, Endosolv R (Endosolv R®), 3% hydrogen peroxide, and 70% isopropyl alcohol. Seven samples per solution were tested and seven samples using water served as controls. One drop of the solution was placed over the set mixture in the canal, and the depth of penetration of a 1.5-mm probe was measured at 2, 5, 10, and 20 min using a dial micrometer gauge. A repeated-measures ANOVA showed a difference in penetration between the solutions at 10 min (p = 0.04) and at 20 min (p = 0.0004). At 20 min, Endosolv R, had significantly greater penetration than 5.25% sodium hypochlorite (p = 0.0033) and chloroform (p = 0.0018); however, it was not significantly better than the control (p = 0.0812). Although Endosolv R, had statistically superior probe penetration at 20 min, the softening effect could not be detected clinically at this time.