Interleukin-1beta, tumor necrosis factor alpha, prostaglandin E2 (PGE2), and Porphyromonas gingivalis-specific immunoglobulin G levels in gingival crevicular fluid were measured in primates immunized with a P. gingivalis vaccine followed by ligature-induced periodontitis. Only PGE2 levels were dramatically suppressed (P < 0.0001) in immunized animals versus controls. A significant correlation (P < 0.027) was also found between PGE2 levels and decreased bone loss scores. This study presents the first evidence of a potential mechanism involved in periodontitis vaccine-induced suppression of bone loss in a nonhuman primate model and offers insight into the role of PGE2 in periodontal destruction.