These studies were designed to determine whether particle phagocytosis could be monitored from the surface of the perfused liver. To achieve this goal, decreases in reflected light were measured during phagocytosis of colloidal carbon particles. Livers were illuminated with 623-nm light via a relatively large fiber-optic light guide (tip diam 2 mm), and reflected light was monitored continuously. A decrease in reflected light was observed when carbon was infused that was proportional to the influent carbon concentration. Initial changes in reflected light were linearly related to rates of carbon uptake by Kupffer cells. Subsequently, rates of carbon uptake were determined from changes in reflected light in periportal and pericentral regions of the liver lobule with miniature fiber-optic light guides. In perfusions in the anterograde direction, rates of carbon uptake were approximately 80% higher in pericentral than periportal regions of the liver lobule. This pattern was reversed when livers were perfused in the retrograde direction. Thus particle phagocytosis predominates in downstream regions of the liver lobule. Because decreasing the pH of the influent perfusate increased carbon uptake, the pH gradient over the liver lobule may be involved in the regulation of particle uptake at the sublobular level.