Cholinergic or generalized heat urticaria is characterized by the onset of small punctate wheals surrounded by a prominent erythematous flare associated with exercise, hot showers, sweating, and anxiety.’ The rash typically first appears about the neck and upper thorax, and when viewed from a distance, it appears as a flush (hives may not be perceived). However, pruritus is a prominent feature of the reaction and, upon close inspection, small punctate wheals can be discerned, sometimes as small as 1 mm in diameter. Gradually the lesions spread distally to involve the face, back, and extremities, and the wheals increase in size. In some patients the hives become confluent and resemble angioedema.’ Also, symptoms of cholinergic stimulation, such as lacrimation, salivation, and diarrhea, are occasionally seen. These various stimuli have the common feature of being mediated by cholinergic nerve fibers that innervate the musculature via parasympathetic neurons and innervate the sweat glands by cholinergic fibers that travel with the sympathetic nerves.” The characteristic lesion of cholinergic urticaria can be reproduced by intradermal injection of 100 pg of methacholine (Mecholyl) in 0.1 ml of saline solution (Fig. 1). When positive, the resultant localized hive surrounded by satellite lesions is indistinguishable from the patient’s spontaneously induced lesions, which confirms the diagnosis. However, we have found that only about one third of patients give a clearly positive skin test, these generally being the most severe cases. Challenge by exercise (e.g., running in a room warmed to 85” C or using a bicycle ergometer for 10 to 15 min) is a far more sensitive test. Thus the skin test can be used to confirm the diagnosis but cannot be used as a diagnostic test.4 Patients who have a positive Mecholyl skin test demonstrate a “hypersensitivity” to cholinergic mediators but show no evidence of an immunoglobulin-mediated allergy to acetylcholine. It is possible that the disorder is due to an intrinsic cellular abnormality that results in abnormal mediator release in the presence of cholinergic agents. A recent