Smoking of alkaloidal cocaine ("crack") has become increasingly prevalent in our society. Recent evidence suggests that crack smoking can cause acute respiratory symptoms, abnormalities in lung function and, in some instances, severe, life-threatening acute lung injury. To evaluate further the relationship between frequent cocaine smoking and respiratory symptoms and lung dysfunction, we studied a sample of 177 heavy, habitual smokers of freebase cocaine (mean 6.6 gm/wk for an average of 27 months) with or without concomitant smoking of tobacco and/or marijuana. Results in this sample were compared with those in a control sample of 75 age-, sex- and race-matched nonsmokers of cocaine who did or did not also smoke tobacco and/or marijuana. After controlling for the use of other smoked substances, heavy, habitual cocaine smoking was associated with the following: (1) a high frequency of acute respiratory symptoms (cough, black sputum, chest pain) in temporal association with freebase use; (2) an obstructive ventilatory abnormality involving the large airways; and (3) a mild but significant impairment in the diffusing capacity of the lung. These findings suggest that heavy, habitual crack smoking produces (1) respiratory tract injury manifested by acute respiratory symptoms and evidence of chronic airflow obstruction in large airways, and (2) an abnormality in diffusion of gas at the alveolar-capillary level. The mechanism of the diffusion defect is unknown but could reflect damage to the alveolar-capillary membrane. Further study of the magnitude, persistence, reversibility, mechanism and clinical significance of the abnormality in diffusing capacity is needed.