We present nine patients with delayed allergic reactions to beta-lactams. Four of them developed reactions to ampicillin; the diagnostic studies suggested the involvement of a type IV hypersensitivity mechanism to an antigenic determinant in the side-chain structure, with intradermal and patch tests positive to ampicillin but good tolerance to benzylpenicillin. Three patients showed delayed hypersensitivity reactions to benzylpenicillin (positive delayed skin tests and/or challenges). Arthus-type reactions were seen in two other patients. Specific IgE of uncertain relationship to benzylpenicillin and ampicillin was later detected in four cases.