A case of unusually severe dermatographism is reported in which baseline plasma histamine levels were repeatedly elevated and histamine release into the circulation was demonstrable upon challenge by scratching the skin. Passive transfer was positive when the patient was challenged after a 48-hr interval, and the responsible factor was heat labile consistent with an IgE-dependent mechanism. Five additional patients with severe dermatographism had elevated baseline plasma histamine levels, but an augmented response upon stroking the skin was not evident. The response of this latter group to antihistamine therapy was excellent; however, the unusual patient described here was only partially responsive. These data suggest that histamine is an important mediator of dermatographism but may not be the sole mediator, particularly when the presentation is of unusual severity. In contrast to patients with cold urticaria and cholinergic urticaria, demonstration of histamine release upon stroking dermatographic patients may be difficult, perhaps because of less total mediator release than that in patients with other physically induced urticarias.