The preservatives benzalkonium chloride (BZC) and potassium sorbate (PS) are widely used in the formulation of nasal drops and cosmetics. Recently, a number of side effects that resulted from mucosal irritation caused by BZC and PS have been reported. Therefore, this study was performed to investigate the possible clinical and histological alterations induced by in vivo administration of these preservatives to the nasal mucosa of rats. 0.01% BZC and 0.12% PS were administered to the nostrils of male rats for 1 or 4 weeks. Clinical symptoms were recorded during the treatment, and light and electron microscopic examinations were carried out on samples taken from one third central and lower regions of the noses at the end of the treatment periods. Symptomatic changes such as sneezing and nasal rubbing were observed in almost all groups, starting from the 6th day of administration. Light and electron microscopy showed histological changes and nasal lesions induced by the preservatives. The symptomatic and histological changes were more pronounced with prolonged duration of administration. Therefore, it has been concluded that in vivo administration of the preservatives BZC and PS may be irritant to the respiratory epithelium of rats. Copyright (C) 2004 S. Karger AG, Basel.