It has been suggested that low-yield cigarettes (LYC) may be less hazardous and that smokers of these cigarettes are exposed to less tar, nicotine, and carbon monoxide. Recent studies have challenged this and question the analysis techniques for measuring yields of these cigarettes. Because published LYC contents may not reflect tissue toxicity and because compensatory puffing behaviors may alter smoke delivery to end-organ tissues, we studied the effect of smoke from a typical LYC on phagolysosome fusion and phagocytosis in alveolar macrophages of rats that chronically inhaled the smoke generated by an intermittently puffing apparatus. Alveolar macrophages were obtained by lung lavage and established in monolayers. Phagolysosome fusion and phagocytosis were assessed using the acridine orange fluorochrome assay. After 8 wk of exposure, there was no difference in phagolysosome fusion between controls and smokers. Carboxyhemoglobin levels in controls versus smokers were 1.36 +/- 0.09% versus 2.13 +/- 0.32% (mean +/- SE) (p = 0.06). A group of animals was similarly exposed, but the side pores of the cigarette filters were sealed with tape to simulate the compensatory behaviors often used by LYC smokers of occluding filter pores with their lips or fingertips. This significantly increased smoke exposure, and the carboxyhemoglobin level of the smokers increased to 7.0 +/- 1.4% (versus controls, p less than or equal to 0.01). Cells from these rats showed alterations in phagocytosis and in phagolysosome fusion compared with alveolar macrophages of control rats. These data suggest that the tobacco in LYC may have toxic effects similar to those of high-yield cigarettes and that LYC are likely to be less hazardous only if smoked in a fashion similar to that of a smoke-generating apparatus.