In the present paper effects of i.p. treatment with free or liposome-entrapped doxorubicin (DXR) on rat peritoneal exudate cell (PEC) populations were examined. Two types of DXR-liposomes were used: one type consisting of egg-phosphatidylcholine/phosphatidylserine/cholesterol (molar ratio 10/1/4, mean size approx. 0.3 micron) and the other type of distearoylphosphatidylcholine/dipalmitoylglycerol/cholesterol (molar ratio 10/1/10, mean size approx. 0.8 micron). Dramatically fewer PEC could be recovered from rats given free DXR or DXR-liposomes i.p. (10 mg DXR/kg body weight) 24 h before sacrifice than from control rats. Also the ratio of leukocyte species was modified by treatment with DXR, in free or liposomal form; in both cases the relative number of macrophages tended to increase. HPLC determination of the amount of DXR associated with monolayers obtained by seeding PEC harvested after a single i.p. dose of free DXR or liposomal DXR suggests that peritoneal macrophages are not particularly active in endocytosing DXR-liposomes. It was observed that the peritoneal macrophages phagocytosed DXR-containing granules from degranulating mast cells after both i.p. treatment with free DXR and DXR-liposomes. Decreased yields of PEC following i.p. treatment with free or liposomal DXR as well as an involvement of mast cells in the processing of both free DXR and liposome-encapsulated DXR in the peritoneal cavity may have important consequences for approaches to i.p. chemotherapy.