Approximately one‐third of the cells in the liver are nonhepatocytes. Of these, the Kupffer cells, or phagocytes lining the sinusoids, are of particular significance since environmental carcinogens must first traverse a Kupffer cell barrier before reaching the liver parenchyma. Phagocytosis and subsequent degradation of carcinogens by Kupffer cells lead to their permanent removal. Factors such as membrane receptors, which determine the avidity of Kupffer cells for various substances, would consequently have a decisive role in the primary interaction between carcinogens and Kupffer cells. Likewise, the intracellular lysosomal apparatus, which determines the ability of these cells to degrade various substances, would determine whether these substances can persist in an active form. In vivo data on Kupffer cell clearance of various substances are plentiful. However, to dissect the complex problem of Kupffer cell interaction with carcinogens, a clear‐cut in vitro system would certainly be useful. A system for separating Kupffer cells from other types of liver cells and maintaining pure Kupffer cell cultures has been achieved in recent years. Some basic cell biological studies—such as studies of membrane receptors and lysosomal enzyme apparatus‐have already been carried out. It could now be rewarding to adopt the system for in vitro studies of Kupffer cell interactions with carcinogens.