The role of stress as a triggering factor in the exacerbation of psoriasis and the clinically symmetric distribution of psoriatic plaques suggested a possible role for neuropeptides in the etiopathogenesis of psoriasis. Several observations by other investigators involving substance P suggested to us a possible role for substance P as a modulator of the inflammatory response in psoriasis. A hypothesis for the role of substance P that would account for the temporal onset with stress, the clinical symmetry of lesions, and the histopathologic features of psoriasis is presented.