Studies of a family with "familial cold urticaria" indicate that the syndrome is not a true urticarial disorder, but appears to be a systemic reaction generated by cooling of the skin. The systemic reaction appears to be mediated by an unidentified humoral substance, probably not histamine. Leukocytosis is a constant accompaniment of the generalized reaction and seems to play a role in the pathogenesis of the skin lesions. The generalized reaction can be prevented by the prior administration of Pseudomonas polysaccharide complex (Piromen).