We have used video time-lapse microscopy to analyze in vitro the interactions of growth cones of newborn rat dorsal root ganglion cells with dissociated young rat CNS glial cells present in the cultures at low density. To provide optimal conditions for neurite extension, cells were grown on laminin and in NGF-supplemented medium. Our initial observation showed that there are 2 subpopulations of growth cones differing in their growth rate on laminin (averages of 12 and 45 microns/hr). When these growth cones encountered astrocytes, they maintained their normal configuration and growth velocity. They subsequently grew along or on top of astrocytes. In some cases, however, fast-moving growth cones showed a slight reduction in their growth rate. When growth cones countered oligodendrocytes, however, firm filopodial contact was sufficient to induce a rapid and long-lasting arrest of the growth cone motility, often followed by a collapse of the growth cone structure. One third of the paralyzed growth cones were observed to retract. Growth arrest and growth cone collapse were strictly dependent on membrane contact between neurons and oligodendrocytes. This contact inhibition phenomenon was exclusively found with differentiated oligodendrocytes and could be prevented by the monoclonal antibody IN-1 directed against neurite growth inhibitors NI-35 and NI-250 (Caroni and Schwab, 1988b). These results confirm previous findings that the neurite growth inhibitor proteins are important in axon outgrowth. Further, the inhibition of neurite growth exerted by oligodendrocytes is a contact-mediated phenomenon that can be triggered by the tip of growth cone filopodia.