The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using both morphometric and electroneurophysiologic techniques. After a standardized localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UMP), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of nerve regeneration for comparison with age-matched crushed or nonoperated controls. Electroneurophysiologic studies of right sural nerves were performed as single fibre measurements. Morphometry was performed on semithin transverse sections of the right common peroneal nerve with a fully automatic interactive image analysis system. Forty days after crush injury the single fibre conduction velocity of all type II afferents in the UMP/CMP treated group was significantly accelerated. There was a trend (10% greater than or equal to p greater than or equal to 5%) to increase of mean efferent single nerve fibre function at this time. Morphometry of nerve fibres revealed a trend to enlargement of mean fibre area and mean fibre diameter related to increased myelin area and myelin thickness. After 60 days, there was a trend to increase of single fibre conduction velocity of all type II afferents in the UMP/CMP treated group. Automated morphometry revealed a significant increase for the following parameters: fibre area, fibre diameter, myelin area, myelin thickness and axon area.(ABSTRACT TRUNCATED AT 250 WORDS)