During a 13-year period, 3256 specimens clinically diagnosed as leukoplakia (('keratosis," "white patch") were submitted to the oral pathology laboratories of Indiana University School of Dentistry and Emory University School of Dentistry. These comprised 6.2% of the tissue specimens processed by these laboratories. The cases were analyzed as to age of occurrence, site of involvement, and pathologic findings. It was found that: leukoplakia occurs chiefly in the 5th, 6th, and 7th decades; about half of the lesions involved the mandibular mucosa, mandibular sulcus, and buccal mucosa; leukoplakia was slightly more common in men (54.2%). Microscopic study showed that 80.1% of the leukoplakias were varying combinations of hyperorthokeratosis, hyperparakeratosis, and acanthosis without evidence of epithelial dysplasia. Mild to moderate epithelial dysplasia was noted in 12.2% of specimens, and severe epithelial dysplasia or carcinoma in situ was found in 4.5%. Infiltrating squamous cell carcinoma was diagnosed in 3.1% of specimens submitted with a clinical diagnosis of leukoplakia. The risk of epithelial dysplasia, carcinoma in situ, or carcinoma varied between the anatomical locations of leukoplakia. The incidence of epithelial alteration, ranging from dysplasia to carcinoma, was 42.9% for lesions of the floor of the mouth, 24.2% for tongue lesions, and 24.0% for lip leukoplakias. The incidence of similar epithelial alterations in other sites varied from 18.8% for palatal lesions to 11.7% for leukoplakias of the retromolar area. The data suggest that there are regional differences in the incidence and character of leukoplakia in the United States. The Emory material, obtained almost exclusively from patients residing in the Southeastern United States, showed a proportionately higher total incidence, a lower male/female ratio, and a greater frequency of epithelial dysplasia, particularly in females, than the Indiana material, which came almost entirely from residents in the Northcentral United States.