Purpose: The purpose of this study was to evaluate the pulpal response of a fluoride-releasing one-step adhesive in nonexposed monkey teeth. Materials and Methods: Cervical Class V cavities were prepared in monkey teeth. The cavities were divided into three groups of different restorative materials. A one-step adhesive (SI-IB551, Shofu) was applied to the teeth, and the cavities were filled with a resin composite (Beautifil, Shofu). In the other two groups, a two-step adhesive (Imperva FluoroBond, Shofu) together with either a resin composite (Beautifil) or a glass-ionomer cement (Fuji II, GC) was placed in the cavities. The teeth were then extracted after 3, 30, and 90 days, fixed in 10% buffered formalin solution, and prepared according to routine histological techniques. Five-micrometer sections were stained with hematoxylin and eosin, or Brown & Brenn gram stain for bacterial observation. Four histological features, odontoblastic change, inflammatory cell infiltrate, reparative dentin formation, and the bacterial staining, were evaluated and compared. The results were compared statistically with significance defined as p 0.05 (Kruskall-Wallis test). Results: Disarrangement of the odontoblasts and slight inflammatory cell infiltrations were the main initial reactions, while deposition of reparative dentin was the major long-term reaction in all groups. No statistically significant differences in the four histological features were seen among the restorative materials placed in the cavities (p > 0.05). No serious pulpal inflammatory reactions, such as necrosis or abscess formation, were observed in any of the experimental groups. Conclusion: The one-step adhesive showed acceptable biological compatibility with the monkey pulp, whereas the pulpal response to the system was minimally different from that of the glass-ionomer cement or the two-step self-etching adhesive. Keywords: one-step adhesive, fluoride, pulpal response