Morphological changes in hepatic macrophages after stimulation were observed with a transmission electron microscope in rats. In the normal liver ruffle formation occupied less than 30% of the cell surface facing the sinusoidal space in 21 of 25 macrophages. When the rats received a dose of carbon tetrachloride, hepatic macrophages 1 day later showed ruffle formation to the same extent as in normal rats. In contrast, in rats 6 days after a dose of Corynebacterium parvum, ruffle formation was intensified, and in 19 of 25 macrophages it was seen to occupy more than 30% of the cell surface (p less than 0.01); 9 of 10 macrophages with more than 70% of the cell surface affected belonged to these rats. Considering that hepatic macrophages at 1 or 6 days after treatment with carbon tetrachloride or Corynebacterium parvum are at the responsive or primed stages, respectively, measurement of the extent of ruffle formation in hepatic macrophages with a transmission electron microscope may provide a useful tool in estimating their stimulatory stage.