We investigated the microglial reaction around cobalt-labeled degenerating neurons and nerve fibers in the frog central nervous system. The aim of these studies was to reveal the routes of migrating microglial cells during debris removal and the effect of seasonal changes on this process in a cold-blooded animal. Oculomotor and spinal motoneurons were filled with cobaltous-lysine complex through their axons. In the torus semicircularis and the isthmic nucleus, neurons were labeled with iontophoretically applied cobaltous-lysine complex through their injured dendrites and axons. The animals were left to survive for 1 to 50 days. During the summer, oculomotor neurons disintegrated by the seventh postoperative day. The debris from the neurons were phagocytosed by microglia-like cells identified by the presence of cobalt in their cytoplasm. Some of these cells were wedged between ependymoglial cells of the cerebral aqueduct, others appeared at the pial surface of the mesencephalon. The speed of this process was twice as fast during the summer as during the winter. Part of cobalt-labeled microglial cells in the torus semicircularis and the isthmic nucleus moved toward the ependyma of the optic ventricle and the cerebral aqueduct, respectively. Cobalt-loaded microglial cells did not move toward the surface in the spinal cord and the deep part of mesencephalic tegmentum, and left the brain probably via blood vessels. We conclude that microglial cells loaded with phagocytosed tissue debris may leave the brain tissue via three routes and their activity depends on the environmental temperature.