OBJECTIVE To assess the effect of respirator type and user characteristics (eg, health status) on the subjective response to respirator use. METHODS The subjective responses for multiple domains were evaluated in 104 volunteers performing work tasks in a simulated work environment. Each used a dual cartridge half face mask and a filtering facepiece (N95) respirator. The study population was recruited to include four groups (normal respiratory status, mild asthma, chronic obstructive pulmonary disease, or chronic rhinitis). Mixed model regression analyses determined the effects of respirator type, disease, gender, and age. RESULTS Half face mask produced more adverse subjective response than the N95 for most scales. There were significant interactions such that disease status modified the effect of respirator type. In general, women reported greater adverse ratings than did men. CONCLUSIONS The effect of respirator type depends on disease status. Respirator design evaluation panels should include persons with mild respiratory disease.