In the present study efforts were made to demonstrate the penetration of topically applied horseadish peroxidase (HRP) through the junctional epithelium of dogs and to study the cellular reactions in normal and sensitized dogs.Three beagle dogs were used. HRP dissolved in saline (5 mg/ml) was topically applied to two jaw quadrants of normal dogs and biopsies obtained after 8 hours. The dogs were then sensitized to HRP>Similar topical applications were carried out in the remaining quadrants and further biopsies taken. The gingival specimens from two dogs were analyzed histometrically with regard to the numerical and volumetric density of inflammatory cells in the junctional epithelium (JE) and subjunctional connective tissue.The histologic and ultrastructural examination showed that topical application of HRP to the gingiva of normal dogs stimulated the accumulation of inflammatory cells in the JE, In sensitized dogs similar HRP application resulted in a six‐fold increase in neutrophils and a two‐fold increase in mononuclear leukocytes. The sensitized dogs also developed and increased volumetric density of inflammatory cells and blood vessels in th subjunctional connective tissue. There was ultrastructural evidence of enhanced phagocytic activity by macrophages accompanied by marked neutrophil degranulat