Three patients are reported on who suffered anaphylactic reactions after amoxycillin (AX) treatment and challenge but tolerated benzylpenicillin (BP) parenterally and orally. Two of the three patients had positive skin tests and RAST to AX reagents but negative responses to benzyl penicilloyl (BPO) specific skin tests and RAST and the minor determinant mixture (MDM) skin test reagent. The third case was negative to all skin tests and RAST. RAST and RAST inhibition on the two positive sera suggest that the response is related to the acyl side chain of AX.