The intraepidermal accumulation of polymorphonuclear leukocytes following the epicutaneous application of leukotriene B4 (LTB4) was studied in lesional and clinically uninvolved skin of five patients with chronic stable plaque psoriasis. The lesions were found to be wholly unresponsive to LTB4, doses of 100 ng failing to produce either micropustules or exocytosis. This phenomenon was sharply localized; the response immediately adjacent to the lesion being identical to that in more distant uninvolved skin. We speculate that both the reduced response to LTB4 in the psoriatic patient and also the tolerance to LTB4 seen after repeated applications, result from the induction of a P450-linked hydroxylase.