It has previously been shown that electrical stimulation of a peripheral nerve induces a release of substance P (SP) from cutaneous nerve terminals. In this study, we investigate whether SP is released from nerve fibre endings in experimentally induced rat saphenous nerve neuromas. The neuromas were induced in pentobarbital anaesthetized rats by ligating and cutting the saphenous nerve 5 weeks prior to the release experiments. The 5-week-old neuromas were desheathed, placed in a perspex chamber, in situ, and superfused with Tyrode solution. The SP-like immunoreactivity (SPLI) content of the superfusate was measured by radioimmunoassay. Addition of 90 microM bradykinin to the superfusate resulted in a calcium-dependent release of SPLI. The other inflammatory mediators, histamine and serotonin, did not induce a release of SPLI. Furthermore, repetitive electrical stimulation of the saphenous nerve (50 V, 5 Hz, 0.5 ms) or superfusion of the neuroma with 50 microM veratridine or 40 mM K+ also failed to induce a release of the peptide. The release of SPLI, induced by bradykinin, from nerve fibre endings in the rat cutaneous nerve neuroma, appears to involve a neurochemical interaction that is independent of electrophysiological excitation.