Deficiency of vitamin A has been shown to cause squamous metaplasia of the epithelium of the tracheobronchial tree. Vitamin A analogues, such as retinoid acid, have been shown to be effective in the treatment of various skin disorders in humans; these compounds have also caused a reduction in the incidence of carcinogen-induced tumors in experimental animals. For these reasons, a clinical trial with orally administered 13-CIS retinoic acid was conducted in 26 patients with varying degrees of cytologic abnormalities in sputum, ranging from moderately atypical metaplasia to overt carcinoma. The drug was administered in daily doses from 1 to 2.5 mg/kg or until toxicity was observed. The cytologic effects of the drug were monitored in sputum. The treatment did not affect the quantitative aspects of sputum cytology. However, degenerative alterations were observed in many of the abnormal cells. Although the experience with 13-CIS retinoic acid reported in this paper is too small for statistical analysis, the cytotoxic effects observed are sufficiently intriguing to suggest further studies in humans and experimental animals.