Purpose: The objective of this study was to histomorphometrically evaluate the synthetic peptide analog P-15 bound to anorganic bovine mineral (Pepgen/P15) in critical-size defects in the rat calvaria. Materials and Methods: A 5-mm-diameter critical-size defect was prepared in 48 rat skulls and divided into 4 equal groups: Pepgen/P15 particles covered by a membrane, Pepgen/P15 particles uncovered, nongrafted membrane-protected sites, and nongrafted uncovered control sites. At 12 weeks, histomorphometric measurements were made of the percentage area of newly formed bone and residual particles, the length of internal and external bone bridging, and linearly, the regenerated marginal and central total tissue augmentation height. Results: Nongrafted, membrane-protected sites gained 60.6% of newly formed bone, followed by 50.6% and 44.2% (P .05 versus membrane only) at the grafted covered and uncovered sites, respectively. All experimental sites contained significantly (P .005) more bone than did control sites (19.9%). In both types of grafted sites, the percentage area of Pepgen/P15 particles was similar. Mean internal and external length of bone bridging at nongrafted membrane-protected sites (76.7% and 71.2%, respectively) was significantly greater (P .005) than that of the grafted covered (43.95% and 51.8%, respectively), grafted uncovered (28.7% and 23.9%, respectively), and control (28% and 25.5%, respectively) groups, except for internal bone bridging in the grafted covered sites. Regenerated marginal and central augmentation heights (0.92 mm and 1.02 mm, respectively) were greatest in the grafted covered group, followed by the nongrafted membrane-protected (0.88 mm and 0.51 mm, respectively), and grafted uncovered (0.89 mm and 0.12 mm, respectively) groups, all of which were significantly greater (P .001) than the control group (0.63 mm and 0.04 mm, respectively). Conclusion: While anorganic bovine mineral/cell-binding peptide contributes in volume, membrane application significantly increases the amount of bone regeneration. Keywords: bovine bone mineral, cell-binding peptide, critical-size defect, guided bone regeneration, histomorphometry, PepGen/P-15