Plasma levels of six protease inhibitors have been measured in patients with chronic urticaria, chronic urticaria with angio-oedema, cold and cholinergic urticaria. In chronic urticaria C1 esterase inhibitor activity was increased compared with a reference control population but there was no detectable abnormality of any other protease inhibitor. Patients with chronic urticaria/angio-oedema showed a reduction in inter-alpha trypsin inhibitor. They also manifested a rise in C1 esterase inhibitor. In cold urticaria there was a significant lowering of alpha 1 antichymotrypsin. The reduction in alpha 1 antitrypsin in this group probably reflects a genetic difference compared with the control population. Patients with cholinergic urticaria also showed a reduction of alpha 1 antichymotrypsin. The elevated levels of alpha 2 macroglobulin in the three groups are probably due to differences in the mean age of these groups compared with the reference population. Comparison of levels of subgroups of patients with and without active lesions suggest that a consumptive effect may contribute to the reduced values, although it seems unlikely to account for them entirely. The results suggest that involvement of pharmacologically active products of protein digestion may be involved in the pathogenesis of urticaria and should prompt attempts to identify these agents and encourage trial of medications which lead to inhibition of proteolytic activity in urticaria.