To investigate the importance of the neuronal cytoskeleton in Schwann cell metabolism, three agents acting on the microfilaments (cytochalasin D, brevine, and phalloïdin) were injected into the endoneurium of rat sciatic nerve. Sciatic nerves were removed 24 h later and separated into two pieces: the first one was the injection site and the second was from nerves located distal to the injection site. The pieces of nerve were incubated with [14C] galactose for 3 h. At the site of injection, [14C] incorporation into monogalactosyldiacylglycerol (MGDG) was perturbed by the three agents, whereas in the distal part, sulfatides and phosphatidylserine were affected by cytochalasin D and brevine. These results show that the three compounds acting on microfilaments have a different effect on Schwann cell metabolism, depending on whether incubated Schwann cells were directly in contact with the toxin or they were only in contact with the axons affected by the toxin. In the latter case, axonal microfilaments seem to be involved in the regulation of Schwann cell metabolism.