To date most studies of the humoral responses in HIV infections have investigated immunoglobulins, the final product of B cell responses. Relatively few studies have examined B cell immunopathogenesis. A number of basic questions are still unanswered (e.g., extent and reason for perturbation of B cell subset changes, including memory B cells and plasma cells, in peripheral blood and tissues). Questions also remain about other potential functional contributions of B cells to HIV infections (e.g., role as antigen-presenting cells). In vivo studies should be performed in the nonhuman primate animal model to determine the emergence of pathologic events in the B cell compartment, in particular in lymphatic and gastrointestinal tissues of naïve and vaccinated animals that are challenged with pathogenic SIV or SHIV. These investigations should be done in parallel to detailed analyses of the magnitude and function of HIV-specific immunoglobulin responses determined in plasma and tissue secretions, and of HIV-specific B cells on a single cell basis.