According to recent concepts, the haptenes responsible for penicillin hypersensitivity are penicillin derivatives rather than the penicillin molecule itself. Penicilloyl-polylysine has been administered as a skin test to 1,022 naval recruits to determine correlation between skin reactions and systemic penicillin allergy. Individuals allergic to penicillin had a 35% incidence of positive skin reactions compared to an incidence of 6.8% in nonallergic recruits. A strongly positive skin test carried an almost ninefold greater risk of occurrence of a systemic reaction following penicillin treatment than did a negative skin test. The test was reproducible and penicilloyl-polylysine in the dosages employed was nonsensitizing.