Chlorcyclizine (CZ) was administered to rats (100 mg/kg, p.o.) for either 1 or 2 weeks (5 days per week). Controls were pair-fed and received deionized water vehicle for the same periods of time. The level of total phospholipid increased about 50% in the lungs after 1 week of CZ but did not increase further after 2 weeks of treatment. There was a time-dependent increase in the recovery of alveolar macrophages (AMs) from the lungs of the CZ-treated rats as well as in the phospholipid content of the cells. After 2 weeks of CZ, the AMs contained 5.6-fold more phospholipid than controls. The AM fraction showed a greater relative elevation in phospholipid at both time points than did the remainder of the lung tissue. The results illustrated the marked susceptibility of the AM to the disruption of phospholipid metabolism by CZ.