To identify and characterize tissue remodeling processes mediated by macrophages, we have generated transgenic mice in which diphtheria toxin is expressed from a macrophage-specific transgene. Expression of the transgene disrupts subsets of mature macrophages in both the eye and the peritoneal cavity and results in the persistence of two normally transient ocular tissues, the hyaloid vasculature and the pupillary membrane. Furthermore, the cells comprising the pupillary membrane appear alive up to 14 days after the structure is normally remodeled, suggesting that the macrophage actively elicits target cell death. Thus, these transgenic mice provide direct evidence for the active involvement of macrophages in developmentally programed tissue remodeling and identify the hyaloid vessels and the pupillary membrane in the eye as targets of macrophage-mediated remodeling.