To investigate the controversy regarding the presence of eosinophils in skin lesions of erythema multiforme, we undertook a retrospective clinicopathologic study of 19 recent cases that fulfilled clinical and histopathologic criteria for the disease. At least a few eosinophils were observed in 13 of 19 cases, and in four cases there were more than three per high-power field, qualifying as "tissue eosinophilia." Immunofluorescence studies in three cases with eosinophils failed to show the linear basement membrane zone fluorescence characteristic of bullous pemphigoid. Giemsa stains revealed that mast cells were present in lesions both with and without eosinophils. The only clinical features that distinguished patients with tissue eosinophilia from those without were an older age of incidence and a longer duration of disease prior to biopsy. Drugs were implicated as a causative factor in some patients both with and without eosinophils, but all four patients with tissue eosinophilia were believed to have drug-induced disease. We conclude that eosinophils do occur in skin lesions of erythema multiforme and are occasionally numerous.