ABSTRACTGuinea pigs primed for delayed type hypersensitivity (DH) to antibiotics such as penicillin G (PCG), carbenicillin (CBPC), sulbenicillin (SBPC), ampicillin (ABPC), cephalexin (CEX), cephalothin (CET) and cephazolin (CEZ) by immunization in mycobacterial adjuvant developed a generalized rash (GR) and flare‐up of previous test sites when challenged peritoneally with high doses of specific antigen. The GR was delayed in time, and histologically characterized by dilated and compacted small vessels and leucocytic infiltrations into the upper dermis. Animals immunized with CEX or CET developed a strong GR despite the absence of detectable antibodies.Hapten‐carrier specificity and cross‐reactivity in the GR system were essentially the same as those observed in skin testing of DH, but differed from those in the hemagglutination system.Accordingly, the GR shares many of the properties of DH skin test reactions: time course, histology, development despite an absence of detectable antibodies, carrier specificity, cross‐reactivity. This experimentally induced rash may be a useful model for delayed type, generalized, exanthematic drug eruptions