Skin testing is reliable and useful to rule out penicillin allergy in most patients who have a history of previous reactions. When we tested 291 inpatients in the University of Washington hospitals for the presence or absence of penicillin allergy, of 97 with a history of penicillin allergy, 12 (12.4%) had positive skin tests. Of 194 patients with no or an unknown history, only 4 (2%) had positive skin tests. Two of the 16 who had positive skin tests (12.5%) reacted only to minor determinant mixtures. Of the skin test-negative patients, 261 were treated with one of the penicillins and only two had any reactions.