Cigarette smoking is strongly associated with functional and morphologic changes in pulmonary alveolar macrophages (PAM). Phagocytic activity is a primary function of PAM, and although the ingestion of particles appears to be normal in the PAM of cigarette smokers, published data suggest that antimicrobial activity of these cells might be diminished. Because phagolysosome fusion (PLF) is an important aspect of the phagocytic process subsequent to the ingestion phase, PLF was evaluated in PAM lavaged from the lungs of male Fisher 344 rats that had been exposed for 8 wk to whole cigarette smoke, to the gas phase of cigarette smoke, or to air as a sham control. Using the acridine orange assay with viable yeast as the phagocytic challenge, we found no difference in the numbers of PAM from each group that had phagocytic activity after a 2-h challenge. However, PLF expressed as the number of orange-fluorescing phagosomes per total number of yeast-containing phagosomes was 35 +/- 1% (X +/- SE) for the group exposed to whole smoke, 53 +/- 2% for the gas phase group, and 65 +/- 1% for the control group. These differences are highly significant, with p less than 0.001 for the whole smoke versus control and p less than 0.01 for the gas phase versus control. Tight phagosomal membranes suggest normal PLF, whereas loose membranes suggest that PLF is inhibited. When the structure of yeast-containing phagosomes was examined and PLF was calculated with the number of phagosomes with tight membranes substituted for the number of orange-fluorescing phagosomes, PLF in smoke-exposed PAM was found to be significantly (p less than 0.01) different from that in sham-exposed control PAM.(ABSTRACT TRUNCATED AT 250 WORDS)