Two patients were studied in whom monoclonal (M) immunoglobulin G (IgG) proteins developed during the course of a serum sickness-like drug hypersensitivity reaction to cloxacillin (Orbenin®) and sodium cephalothin (Keflin®), respectively. The clinical evidence and time sequence of events support this association. In both patients there was evidence of an active antibody response to the given antibiotic and to the benzylpenicilloyl group as well. However, protein fractions obtained by agar gel preparative electrophoresis failed to show a higher antibody concentration where the M peak was located, and absorption experiments performed with penicillin G-, cloxacillin- and cephalothin-coated red cells failed to absorb these M proteins. These transient paraproteins can be seen in association with antibiotic(s) administration in the context of a hypersensitivity reaction and do not apparently represent a specific immune response.