Previous work has shown that alveolar macrophages (AM) from human immunodeficiency virus (HIV)-infected patients are superior accessory cells (AC) and secrete greater amounts of T cell-stimulatory cytokines than do normal AM. We now examine the role of AM-T cell adherence in AM AC function by examining the ability of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) to block adherence and lymphoproliferation. Mitogen-induced (concanavalin A, pokeweed mitogen) adhesion and proliferation were studied in the presence and absence of mAb directed against beta 2 integrins and ICAM-1. AM from normal subjects and HIV-positive patients were used as AC, and normal T cells were used as responders. Normal and HIV AM bound equal numbers of T cells under similar conditions. Adherence was blocked by antibodies to beta 2 integrins and ICAM-1 in both groups. Con A-induced lymphoproliferation was positively correlated with adherence in normal volunteers. In contrast, greater Con A-induced AM-T cell adherence in HIV-positive patients was associated with worse AC function. Antibodies that impaired AM-T cell adherence completely inhibited AC function in both groups when added at the beginning of mitogen assays, indicating that initial contact was required. However, the addition of antibodies after 4 h inhibited lymphoproliferation less in HIV-infected individuals than in normal volunteers, suggesting that prolonged AM-T cell adherence was less important for optimal AC function in these patients. Using these and previous results, we present a model for AM AC function in normal volunteers and HIV-infected individuals.