The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12- step desensitization protocol and to characterizethe immune mechanism of carboplatin HR. We analyzed 10 consecutive patients who had documented HR to carboplatin and in whom continued treatment with carboplatin was considered advantageous. The patients were treated with carboplatin using a 6- h, 12- step desensitization protocol with a 30- min premedication regimen. Skin tests were performed on five patients. Ten patients successfully completed 35 planned courses of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symptoms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequent courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to carboplatin, four had positive wheal and flare reactions. In one patient, the skin test response to carboplatin became negative after desensitization. The 6- h, 12- step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to carboplatin suggest a mast cell/IgE mediated mechanism. Conversion of the positive skin test to a negative response after desensitization supports antigen specific mast cell desensitization. The incidence of hypersensitivity reactions (HR) is increased in patients treated with multiple courses of carboplatin. The purposes of this investigation were to evaluate the effectiveness of a 12-step desensitization protocol and to characterizethe immune mechanism of carboplatin HR. who had documented HR to carboplatin and ingenous continued treatment with carboplatin was a advantaged. The patients were treated with carboplatin using a 6-h, 12-step desensitization protocol with a 30- min premedication regimen. Ten patients successfully completed plan of desensitizations to carboplatin, 31 of which were without reactions. Four patients had symptoms during their first (n = 3) and third (n = 1) desensitizations but tolerated the re administration of infusions without further reactions. For subsequent courses, the protocol was modified for two patients who had extracutaneous symp toms during desensitization and was unchanged for the patient who had mild urticaria. These three patients tolerated subsequently courses of desensitizations without reactions. The fourth patient with symptoms during desensitization no longer required carboplatin due to progressive disease. Of the five patients who were skin tested to In one patient, the skin test response to carboplatin became negative after desensitization. The 6-h, 12-step desensitization protocol is safe and effective for treating patients with carboplatin HR. Positive skin tests to Conversion of the positive skin test to a negative response after desensitization of support antigen specific mast cell desensitization.