To learn more about neuropeptide-induced glial responses which accompany axon regeneration, we studied effects of VIP on laminin production by cultured Schwann cells. Schwann cells were isolated from sciatic nerves of neonatal mice, purified, and incubated for 5 days in either control medium (DMEM + 15% FCS) or control medium containing 10-7-10-'1 M VIP. At and lo-' M VIP, laminin levels measured by enzyme-linked immunosorbent assay were significantly higher (55% and 35%) than those in control cultures. Lower VIP concentrations (10-9-10-" M) produced smaller increases which were not significant. Low-affinity VIP receptors which mediated this effect were demonstrated on Schwann cells by radioligand binding studies. The increased Schwann cell synthesis of laminin induced by VIP was blocked when either a VIP antagonist or a VIP receptor antagonist was added to the VIP-containing incubation medium. In contrast to astrocytes, when Schwann cells were loaded with fura-2, VIP did not increase cytosolic Ca2+. This indicates that Schwann cells and astrocytes may have different intracellular transduction pathways; their receptor subtypes also may differ. We suggest that the VIPinduced increase in laminin synthesis which we have observed in cultured Schwann cells may also occur in vivo and might be an important component of axon-Schwann cell interactions during nerve regeneration.