We designed a prospective and retrospective study to determine the incidence of allergic contact dermatitis to topical application of fluorouracil. Intracutaneous and epicutaneous skin tests of various fluorouracil concentrations were given to patients who were to be treated with the drug for actinic keratoses (group A) and to patients who had previously been treated with fluorouracil for actinic keratoses (group B). Six patients in group B had allergic contact dermatitis to topical fluorouracil. The common clinical characteristic of the six patients was a severe pruritic eruption at the site of fluorouracil application. Allergic contact dermatitis should be suspected in the presence of severe pruritus or a severe eczematous response in patients treated with topical fluorouracil.