Blockade of phagocytosis and selective elimination of macrophages (m phi s) are generally accepted procedures for gaining knowledge about the function of m phi s in vivo. This study demonstrates that intravenous injection of gadolinium chloride (GdCl3) not only blocks phagocytosis by rat liver m phi s (Kupffer cells) but also selectively eliminates the large m phi s situated in the periportal zone of the liver acinus. Repopulation of m phi s starts at 4 days after injection. During repopulation, m phi s are less vulnerable to GdCl3. When repopulation is complete, the new m phi s show the same vulnerability as the original ones. Splenic m phi s are less vulnerable to GdCl3 because only some of the red pulp m phi s transiently disappear. The white pulp m phi s are not affected. Repopulation occurs sooner than in liver. These results indicate that administration of GdCl3 is a suitable approach to studying the in vivo function of large Kupffer cells.