Biopsy specimens from lesional and uninvolved skin of nine patients with delayed pressure urticaria, three patients with acute urticaria, six patients with chronic recurrent urticaria, and four patients with urticaria pigmentosa were analyzed by routine histology and by immunochemistry for their reactivity with monoclonal antibodies to three different subsets of macrophages. Skin from 12 healthy volunteers served as control. Uninvolved skin of patients did not differ from that of healthy volunteers. An antibody against activated macrophages (27E10) was reactive to a marked extent with macrophages in wheals of pressure urticaria, more variably in acute and chronic urticaria, and practically not at all in urticaria pigmentosa. Antibodies with specificities for macrophages in healing (RM3/1) and normal (25F9) tissue reacted more markedly in all but pressure urticaria lesions, compared with normal skin. These findings indicate an active involvement of inflammatory macrophages in whealing reactions while these cells play apparently no role in cutaneous mast cell proliferation (urticaria pigmentosa).