Methylene chloride is used as softening agent for guttapercha and as adhesion promotor for polymethylmethacrylate (PMMA). However, methylene chloride has been found to be carcinogenic. It was the aim of the present work to search for harmless substitutes for methylene chloride in these situations. A number of possible candidates with structural similarities to guttapercha or PMMA were selected. The efficacy in softening of guttapercha of these compounds was measured by the depth of penetration of a needle under the load of 2 N. The effect of the compounds on the adhesion between PMMA and an acrylic rebasing material was measured in shear. It was found that a number of alkenes or dialkenes of moderate molecular weight (1,3-pentadiene, cyclopentene, isoprene, 2-methyl-2-butene, and 1,5-hexadiene) were as effective as methylene chloride as softening agent for guttapercha. As adhesion promotor in bonding to PMMA, it was found that low molecular weight methyl esters (methyl formate and methyl acetate) were as effective as methylene chloride. Because of the variation in polarity, the calculated solubility parameter was not a reliable predictor of softening efficacy of the investigated compounds.