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A case of an anaphylactic shock following topical application of chlorhexidine preparation is reported. Specific skin-sensitizing antibodies against chlorhexidine were demonstrated in the serum from the patient by a passive transfer test. IgE antibodies against chlorhexidine were also detected hy radioallergosorbent technique (RAST). Paper discs conjugated with chlorhexidine-HSA (human serum albumin) significantly bound the IgE antibodies. Furthermore, all of the sera from seven other patients with shock reactions following the topical application of chlorhexidine preparation also showed high RAST counts. Both chlorhexidine gluconatc and chlorguanide which represents approximately half a molecule of chlorhexidine inhibited the reaction in a dose-dependent fashion. It is suggested that the shock reactions following topical application of chlorhexidine are mediated by IgE antibodies against chlorhexidine and that chlorhexidine and chlorguanide share the same antigenic determinant.