Collagenase-isolated pancreatic islets from C57BL/6J mice were cultured overnight and transplanted under the kidney capsule of non-diabetic syngeneic hosts. Cryostat sections of grafts and fresh islets were stained for acetylcholinesterase (AChE) and vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI). Immediately after isolation, as well as 2-5 days after transplantation, VIP-LI- and AChE-positive nerve cell bodies were clearly seen in the periphery of the islets. Grafts 3-5 days old exhibited a transient and marked increase in VIP-LI nerve cell bodies and fibres. Seven days after transplantation VIP-LI nerve structures began to decrease in number and after 26-52 weeks they were no longer detectable. In contrast, AChE-positive nerve cell bodies and fibers, which showed a relatively constant pattern of distribution, were observed throughout the entire observation period. Restaining experiments demonstrated the coexistence of VIP-LI and AChE activity in the neurons. It is concluded that the grafts were extensively equipped with an intrinsic VIP-ergic and AChE-positive innervation. The initial, transient enhancement of VIP-LI expression probably reflects an adaptation of the neuro-insular complex to the preganglionic denervation, or to the ectopic environment, or both.