Liposome-entrapped dichloromethylene diphosphonate (Cl₂MDP) was injected locally into the thymus of adult rats. This treatment, which has been found to deplete resident macrophages in other organs, also reduced the number of thymic macrophages. The depletion was evident in the cortex and the corticomedullary zone at 5, 13 and 23 days after Cl₂MDP treatment, while the decrease in medullary macrophages only became significant 13 and 23 days after injection. However, the maximal reduction of macrophages was evident 13 days after this treatment. Thirty-five days after Cl₂MDP treatment, macrophages repopulated the thymus. Our results suggest that the cortical and cortico-medullary macrophages have a high phagocytic activity consistent with their predominant role as scavengers of the large numbers of thymocytes that die under physiological conditions. It is concluded that liposome-mediated depletion of thymic macrophages can serve as an experimental model to study the roles of these cells.