The response of neonatal rat locus coeruleus neurons to contact with myelin extracts prepared from the CNS and PNS was examined. The growth cones of these neurons collapsed following contact with central myelin, but continued to elongate on contact with peripheral myelin. Central myelin elicited an increase in the intracellular free calcium concentration in these growth cones, while peripheral myelin did not. This increase appeared to require transmembrane calcium flux, since it was blocked by extracellular EGTA, and also by extracellular cobalt. These neurons express N- and L-type calcium channels. Exposure to 5 microM omega-conotoxin GVIA, a specific blocker of N-type channels, prevented both the myelin-evoked increase in growth cone calcium concentration and the collapse of growth cones.