Multiple myeloma (MM) is twice as common among Blacks than Whites in the United States. The reasons for this racial disparity are unknown, and the etiology of this cancer, in general, is poorly understood. Repeated or chronic antigenic stimulation (CAS) of the immune system has been suggested as a risk factor. Previous case-control studies have reported inconsistent CAS associations based on evaluations of individual and biologic categories of medical conditions. Interview data from 573 cases and 2,131 population-based controls were used to investigate further the CAS hypothesis using an immunologically based approach, and to determine whether CAS accounts for the excess of myeloma among Blacks. Over 50 medical conditions were grouped into biologically and immunologically related categories, and B-cell- and T-cell-mediated response groups. Except for urinary tract infections among Black men (odds ratio [OR] = 2.0), no significantly increased risks of MM were observed. However, there was a suggestion of increased risk among Blacks with an increased exposure to anaphylactic conditions. Analysis by immunoglobulin type revealed significantly elevated risks of IgG myeloma with eczema (OR = 2.1), the biologic category 'allergic conditions' (OR = 1.6), and the immunologic category 'anaphylaxis response' (OR = 1.6) among Whites, with Blacks having slightly lower risks. Our findings do not support a causal relationship between CAS and MM, nor do they explain the higher incidence among Blacks.