A study was undertaken to verify the reliability of the Tzanck test, performed both by traditional cytomorphology and by a direct immunofluorescence technique, for the diagnosis of oral pemphigus vulgaris. Cytologic smears were obtained from oral erosions of 129 patients with various bullous diseases of the oral mucosa, clinically suspected of being oral pemphigus, as well as from 30 healthy subjects. The 40 cases with subsequent histologic proof of oral pemphigus were cytologically diagnosed as such, based on the significant cytomorphologic findings of acantholytic cells or on the pericellular deposition of IgG (which persisted after cytocentrifugation) in epithelial cells, as studied by direct immunofluorescence. Cytomorphology gave positive results in 37 patients with pemphigus and in one patient with a final diagnosis of herpetic stomatitis and gave negative results in all other cases. Immunocytology gave positive results in all patients with pemphigus and negative results in all other cases. The findings indicate that cytomorphologic studies may be useful in screening suspected cases of oral pemphigus vulgaris while the immunocytologic test may provide a reliable definitive diagnosis.