The effect of 5-fluorouracil (5-FU) on murine monocytes and macrophages was the subject of this study. This drug strongly decreased the levels of all types of peripheral blood cell, but had no effect on the composition and cellularity of peritoneal exudate or the expression of Ia antigens or phagocytic activity of peritoneal macrophages. The pinocytic activity of normal macrophages was unchanged, but the pinocytosis of thioglycollate-stimulated macrophages was significantly reduced. The expression of Fc receptors was influenced only after the first day after 5-FU injection. The clearance and organ distribution of radioactive labeled antigen was also not changed. Our findings suggest that tissue macrophages are resistant to 5-FU, but the results obtained with stimulated macrophages suppose differential susceptibility of macrophages. We presume that the immunosuppressive action of 5-FU results from selective depletion and suppression of T and B lymphocytes rather than from changes in immunoregulating functions of macrophages.