In 12 zoster patients who had developed postherpetic neuralgia with dynamic mechanical allodynia and in six zoster patients who had recovered without pain, the functional role of nociceptive C-fibers in allodynia was assessed by quantifying axon reflex reactions induced by histamine iontophoresis within allodynic regions and in their contralateral sites. In patients with postherpetic neuralgia, histamine responses were reduced or abolished within allodynic areas, indicating degeneration of nociceptive C-fibers. In patients who recovered without pain, histamine responses were bilaterally identical, indicating complete regeneration of nociceptive C-fibers. These results demonstrate that sensitized nociceptive C-fibers are not involved in signaling and maintenance of allodynia. Alteration in CNS processing may reorganize synaptic ties between central pain-signaling pathways and mechanoreceptive A beta-fibers depending on afferent C-fiber degeneration rather than ongoing C-fiber input.