1 The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2 Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused the release of PGD2 and histamine, but not PGE2, from the skin of the atopic subjects. The molar ratio of histamine to PGD2 was about 140: 1. Control subjects were unresponsive. 3 PGD2 was released from passively sensitized human skin challenged with antigen in vitro. The time course was similar in vitro and in vivo. The ratio of histamine to PGD2 in vitro was 78: 1. 4 The identities of the prostaglandins were confirmed by high performance liquid chromatography and radioimmunoassay to PGD2 and PGE2. 5 PGD2 is the major arachidonic acid cyclo-oxygenase product synthesized by human mast cells. It is pro-inflammatory in human skin but its functions as a mediator in immediate hypersensitivity reactions in human skin are not clear. The results of this study suggest that, relative to histamine, PGD2 contributes little to the oedema and erythema of immediate reactions in human skin.