The decrease in the swelling capacity and the length of the refractory period after nonimmunologic contact urticaria produced by one application of six human nonimmunologic contact urticaria agents was studied with the use of the guinea pig ear test. On retesting 1 day later, all substances (benzoic acid, cinnamic acid, cinnamic aldehyde, diethyl fumarate, methyl nicotinate, and dimethyl sulfoxide) showed reactions decreased by at least 50%. This decrease was most marked with cinnamic aldehyde (91% decrease), cinnamic acid (88%), and benzoic acid (86%). The tachyphylaxis was not specific to the substance producing it; reactivity to other contact urticaria agents decreased as well. The refractory period was 4 days after methyl nicotinate, 8 days after diethyl fumarate and cinnamic aldehyde, and 16 days after the other agents. These results suggest the following practical application: there is a need for (1) appropriate scheduling in the reuse of animals for testing for nonimmunologic contact urticaria and (2) an awareness of possible false-negative results in human tests for this form of urticaria because of tachyphylaxis.