We performed flexible fiberoptic bronchoscopy in 29 habitual, heavy marijuana smokers 25 to 45 yr of age, with and without concomitant tobacco smoking, to inspect and biopsy their proximal tracheobronchial tree for the evaluation of histopathologic changes. Control tobacco smokers (TS) and nonsmokers (NS) residing in the same metropolitan area were similarly studied and compared with the marijuana smokers (MS) and marijuana-tobacco smokers (MTS). Respiratory and drug histories, physical examination, and pulmonary function tests were obtained prior to bronchoscopy. The prevalence of respiratory symptoms and pulmonary function abnormalities was generally higher in the 3 smoking groups than in the NS group but was not statistically different across all groups. However, bronchoscopic inspection revealed airway hyperemia and other visible abnormalities in 32 (91%) subjects in the 3 smoking groups, unlike the unremarkable findings in the NS group. Light microscopy showed 2 or more histopathologic changes in the bronchial epithelium of all MS, MTS, and TS. Squamous metaplasia was observed in all MTS, a prevalence that was significantly different from that in MS, TS, and NS. Hyperplasia of basal and goblet cells was more prevalent in the MS than in the NS, whereas cellular disorganization was more prevalent in the MS than in the TS. A direct relationship between cumulative marijuana use (joint-years) and bronchoscopic and histopathologic changes was not apparent in this study sample. These results indicate that relatively young, habitual, heavy marijuana smokers have a high prevalence of abnormal airway appearance and histologic findings, irrespective of concomitant tobacco smoking.(ABSTRACT TRUNCATED AT 250 WORDS)