Neurogenic inflammation and other local efferent functions of the capsaicin-sensitive nerve endings is well established. Here, we describe evidence for a systemic neurogenic anti-inflammatory effect initiated in the rat by this local response. A preceding local neurogenic inflammation induced by antidromic stimulation of lumbar dorsal roots inhibited a subsequent inflammatory response due to antidromic stimulation of the contralateral dorsal roots or evoked by subplantar carrageenin injection or instillation of capsaicin solution into the eye. Initiation of these anti-inflammatory responses were prevented by degeneration of the capsaicin-sensitive afferents after perineural capsaicin pre-treatment, but not by bilateral adrenalectomy. These results demonstrate an unorthodox new type of neurohumoral regulatory mechanism of sensory fibres and provide a possible mode of action for the anti-inflammatory effect of counter-irritation and acupuncture.