Injection of dithizone, a zinc chelating agent, induced selective killing of intestinal Paneth cells within a few min by forming toxic insoluble zinc-dithizonate complexes. However, regeneration of Paneth cells took place right after dithizone treatment and resumed the normal level as early as 72 hr with over-shooting persistent for 2 weeks. The process or regeneration in intestinal crypts was studied by means of morphology, uptake of the thymidine analog 5-bromo-2′-deoxy-uridine and immunohistochemical staining of Paneth cell differentiation markers such as lysozyme and zinc-binding proteins. It was found that Paneth cells regenerated without cell division and DNA synthesis apparently by direct transformation of non-Paneth crypt base columnar cells. Dithizone induced a transient wave of cell growth in all compartments of the intestinal crypt.