Results in this sample were compared with those in a control sample of 75 age-matched, sex-matched, 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 a high frequency of acute respiratory symptoms in temporal association with freebase use, an obstructive ventilatory abnormality that involves the large airways, and a mild but significant impairment in the diffusing capacity of the lungs. These findings suggest that heavy, habitual crack smoking produces respiratory-tract injury manifested by acute respiratory symptoms and evidence of chronic airflow obstruction in large airways, and 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. 1 figure and 32 references