The healing of standardized bone defects grafted with either particulate ionomeric or hydroxyapatite bone substitutes was compared in the mandibular ramus of 30 Sprague-Dawley rats. The possible additional response achieved when combining these materials with a guided bone regeneration (GBR) technique was also evaluated. Three groups of 10 animals received either no implant material or ionomeric or hydroxyapatite bone substitute in defects in the right ramus. The left mandibular defects received the same treatment, except that the operation site was covered by a membrane (GBR technique). Half of the animals were sacrificed at 4 and 10 weeks following surgery, and the inflammatory response at the implant site and the amount of new bone formed in the defects were determined histomorphometrically. Defects implanted with ionomeric bone substitute exhibited more bone formation (4 weeks = 3.19 ± 0.38 mm2, 10 weeks = 5.35 ± 0.26 mm 2) than both defects that received no treatment (4 weeks = 0.88 ± 0.35 mm 2, 10 weeks = 2.1 ± 0.49 mm 2), membrane alone (4 weeks = 1.21 ± 0.05 mm 2) or hydroxyapatite bone substitute (4 weeks = 1.41 ± 0.46 mm 2, 10 weeks = 3.34 ± 0.41 mm 2) at 4 weeks (P .01) and at 10 weeks (P .05). The use of a GBR technique did not increase the amount of bone formed, compared to the use of bone substitutes alone. Hydroxyapatite and ionomeric bone substitutes used alone were more effective in inducing repair of the defects than was GBR membrane alone. The use of hydroxyapatite was associated with a greater inflammatory reaction (P .01) than was ionomer in this model. Keywords: bone regeneration, glass-ionomer cement, hydroxyapatite, ionomeric