An electrophysiological method was used to measure the potassium permeability (PK) of the perineurium of the sciatic nerve of frogs Rana temporaria and R. pipiens. Isolated but intact nerves were mounted in a grease-gap chamber, and compound action potential and DC potential monitored. Change in the DC potential (delta DC) in response to challenge with 100 mM [K+] Ringer was used to assess the K+ permeability of the perineurium, since change in DC potential under these conditions reflected changes in the axonal resting potential. The permeability of the perineurium was calculated from the published calibration curve relating delta DC to bathing [K+] in desheathed nerves of Abbott et al. (1997). In the control condition, PK was < 1.1 x 10(-6) cm.s-1. The bile salt sodium deoxycholate (DOC, 1-4 mM) caused a dose-dependent increase in PK, which reached a maximum of 1.7 x 10(-5) cm.s-1 after 2-min exposure to 4 mM DOC, but access of K+ to the endoneurial compartment was more restricted after DOC than after desheathing. Protamine phosphate (1 mM) and protamine sulphate (0.1-5 mg/ml equals 0.125-6.25 mM) had no effect on PK. Neither histamine (0.4-40 mg/ml), bradykinin (0.1-5 mg/ml) nor serotonin (5-hydroxytryptamine, 0.1-5 mg/ml) affected PK. The frog nerve perineurium appears to be relatively insensitive to chemical agents and inflammatory mediators, in contrast to the endothelial cells forming the endoneurial blood-nerve barrier and the blood-brain barrier.