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When rats were treated with chlorphentermine, a cationic amphiphilic drug, a phospholipid storage disorder developed in alveolar macrophages, the severity of which was directly proportional to the duration of treatment over a 4-week period. Concomitantly, a progressively greater percentage of the cells became multinucleated such that, after 4 weeks of drug treatment, 18 per cent of the cells contained more than one nucleus. Greater than 99 per cent of the macrophages from control rats had on nucleus per cell. Associated with the multinucleation was an increase in the DNA, RNA, and protein content of the macrophages and increases in the RNA to DNA and protein to RNA ratios relative to cells from untreated rats. Centrifugal elutriation was employed as a means to study the multinucleation as a function of increasing cell size. At each of the 4 weekly intervals studied, the percentage of cells with two or more nuclei increased as the cells became larger. An increase in multinucleation was also found in cells of any given size range as the time of treatment increased. Possible mechanisms responsible for the multinucleation phenomenon are discussed.