Surfactant proteins (SP) play an important role in enhancing the surface properties of pulmonary surfactant and participate in host-defense mechanism(s) of the lung. Although it is known that cigarette smoking alters both pulmonary surfactant lipid composition and function, its effect on SPs is unknown. The present study was carried out to determine if chronic exposure to cigarette smoke alters pulmonary SPs, namely, SP-A and SP-B, in a rat model. Sprague-Dawley rats were exposed to cigarette smoke in a nose-only exposure system twice a day, every day for 70 weeks. At termination, bronchoalveolar lavage (BAL) fluid and the lung tissues were collected from room control, sham-treated (SH), and smoke-exposed (SM) animals for analyses. The total protein levels in the BAL fluid of SM rats tended to be higher but were not statistically different from those of the SH group. However, the albumin content of BAL fluid in SM rats, measured by quantitative immunoblotting, was significantly higher than in control groups. Compared to control groups, SP-A and SP-B levels in the BAL fluid of SM rats were significantly reduced by 25 and 50%, respectively, when expressed as units per microgram of BAL fluid protein. However, when calculated as total BAL fluid SP recovered per rat, only the SP-B levels of SM rats were significantly different from the control groups. Further analysis by ELISA confirmed the reduced levels of SP-B in SM rats. In contrast to BAL fluid, the lung tissue levels of SP and their respective mRNAs were not significantly different between the control and smoke-exposed groups. These results show a selective reduction in SP-B content on the bronchoalveolar surface following chronic exposure to cigarette smoke and suggest an inhibitory effect of cigarette smoke on surfactant secretory processes and/or a localized destruction of SPs on the bronchoalveolar surface.