The involvement of the sympathetic postganglionic neuron in secondary hyperalgesia was evaluated using a model of secondary hyperalgesia induced by a small intradermal injection of capsaicin in the rat, a procedure known to produce mechanical hyperalgesia/allodynia in humans. Capsaicin injection into the glabrous skin of the hind paw led to increased sensitivity to mechanical stimulation with von Frey filaments at the injection site (i.e. primary hyperalgesia) as well as in an area of the hind paw remote from the site of injection (i.e. secondary hyperalgesia). Surgical removal of the sympathetic postganglionic neurons innervating the hind paw plantar skin before the capsaicin injection prevented secondary hyperalgesia. However, decentralization of the sympathetic postganglionic neurons subserving the hind paw did not effect secondary hyperalgesia. Phentolamine, an alpha-adrenergic receptor antagonist, as well as prazosin, an alpha 1-adrenergic receptor antagonist, given systemically, both blocked the development of secondary hyperalgesia. Yohimbine, an alpha 2-adrenergic receptor antagonist, was without effect. Prazosin also blocked the development of secondary hyperalgesia when given intradermally at the site of capsaicin injection. Activation of C-fibres with capsaicin induces secondary hyperalgesia, which is sympathetic postganglionic neuron-dependent. This sensory-sympathetic interaction is, however, independent of preganglionic sympathetic outflow and seems to be mediated by an alpha 1-adrenergic mechanism. Sensory-sympathetic interaction appears to take place in the area of capsaicin-induced C-fibre nociceptor activation.