Use of cocaine by smoking its alkaline precursor ("freebasing") has become increasingly prevalent. Recent studies of small numbers of cocaine users suggest that freebasing frequently causes cough, dyspnea, and abnormalities in diffusing capacity (DCO), although these findings could have been due to concomitant use of other drugs. We therefore evaluated the relationship between cocaine use by freebasing and chronic respiratory symptoms and lung dysfunction in a large sample of habitual smokers of marijuana with or without tobacco who denied intravenous drug abuse. The findings suggested that, among habitual marijuana smokers, "moderate" cocaine smoking damaged both large and small airways, as reflected by functional changes that were independent of concomitant marijuana use and appeared to be synergistic with the effects of tobacco. On the other hand, no adverse influence of cocaine smoking on the pulmonary microcirculation was demonstrated in our sample of freebase users.