The usual battery of skin tests employed for determining penicillin allergy may fail to detect allergic reactions to side chain-specific beta-lactam agents. We report the cases of six patients who experienced anaphylactic reactions after treatment and challenge with amoxicillin but who tolerated parenteral challenges with benzylpenicillin, aztreonam, and ceftazidime. Results of skin tests for amoxicillin (10 mg/mL) were positive for four of the six patients.