We have investigated whether chronic nerve growth factor (NGF) depletion affects the development of transmedian collateral reinnervation by C-fibres. Using a dye-labelled plasma extravasation technique in rats, the extent of transmedian innervation of the skin by C-fibres in the inferior alveolar nerve (IAN) was determined 8-10 weeks after sectioning and preventing regeneration of the contralateral IAN. Another group of animals were immunised against NGF prior to the nerve section and a third group acted as unoperated controls. A small but significant transmedian collateral reinnervation by C-fibres developed after contralateral denervation alone, but was not found in the animals also immunised against NGF. These results suggest that NGF is essential for the development of collateral reinnervation from cutaneous C-fibres.