The aim of the present study was to examine whether inhibition of the microglial cell reaction around axotomized motoneurons affects the subsequent regeneration process of the injured axons. The microglial cell reaction in the hypoglossal nucleus of the rat was blocked by infusion of cytosine-arabinoside (ARA-C) into the ventricular system. Axon regeneration was evaluated by determining the number and size distribution of myelinated axons at a defined level distal to the crush site, the number of neurons which could be retrogradely labelled from the distal stump as well as the number of motor endplates in the tongue at various times following injury. No significant difference was observed for any of these parameters between ARA-C-treated and untreated animals. Therefore, it is concluded that the microglial cell reaction is not necessary for peripheral nerves to regenerate and restore target contact at a normal rate and to a normal extent.