Introduction: Systemic steroids have been associated with anergy. Treatment with high-dose inhaled steroids has many documented systemic side effects, including adrenal suppression, reduction in growth velocity, and increased bone metabolism; however, little is known about their effect on delayed-type hypersensitivity (DTH). Study objectives: The purpose of this study was to determine if a 28-day course of high-dose inhaled fluticasone suppresses DTH to a standard panel of antigens. Methods: Forty-five healthy, steroid-naive subjects volunteered for this randomized, double-blinded, placebo-controlled trial. All subjects bad baseline DTH assessed by intradeimal skin testing to a standard panel of antigens (tetanus, candida, mumps, and tuberculin) read 72 h after placement. Subjects were then randomized to receive placebo or high-dose inhaled fluticasone (880 mug/d) for 28 days, after which a second DTH panel was performed. A third DTH panel was performed after a 30-day washout period. Measurements and results: Of the 45 enrolled subjects, 38 subjects completed the study, including 20 subjects in the placebo group and 18 subjects in the drug group. There was no significant difference in the amount of induration between drug and placebo groups for any of the three periods tested. Conclusion: Twenty-eight days of treatment with high-dose inhaled fluticasone did not suppress DTH in healthy volunteers.