By examination of compound action potentials in the saphenous nerve of the anaesthetized rat it has been shown that capsaicin causes a rapid, dose-dependent, failure of conduction in many C-fibres when applied directly to the nerve. A large reduction in C-fibre conduction occurs with concentrations as low as 110 microM. After a 15-30 min exposure to capsaicin, only partial recovery occurs in 1 h. Similar block of C-fibre conduction occurs in the ferret. However, only smaller, reversible, reductions in C-fibre conduction were seen in the guinea-pig and rabbit, even at the highest concentration of capsaicin used (33 mM). A small reduction in the A delta component of the compound action potential occurred in all four species. In the rat and ferret the effects were much less than those on C-fibres. At high doses, small reversible effects were also seen on the fastest conducting A alpha beta component of the compound action potential in the rat, rabbit and guinea-pig; no effects were seen on the A alpha beta fibres in the ferret. Decreases in amplitude of the compound action potential were accompanied by some slowing of conduction in most cases. The slowing was less than 5% except for the rat A alpha beta and C-fibres and the ferret C-fibres where 9-15% changes occurred at the highest doses of capsaicin. Opening the connective tissue sheath of the nerve did not significantly increase the effectiveness of capsaicin.