We have developed an isolated spinal cord-skin preparation of the newborn rat. The spinal cord together with a piece of skin connected to the cord by the saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were recorded extracellularly from the third lumbar ventral root. Application of capsaicin (0.5-2 microM) or KCl (60-350 mM) with brief pressure pulses to the perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration in the ventral root. The response was depressed by [Met5]enkephalin (0.03-3 microM), morphine (0.1-2 microM) and a tachykinin antagonist, [D-Arg1,D-Trp7,9,Leu11] substance P (spantide), (1-10 microM), applied to the spinal cord by superfusion, whereas the response was augmented by centrally administered calcitonin gene-related peptide (0.1-0.2 microM) or bicuculline (0.5-1 microM).