T lymphocytes from a majority of patients with urogenital gonococcal disease (67%-80%) proliferated on incubation with gonococcal porin (Por), compared with minimal induced proliferation of T lymphocytes from normal volunteers. A significant increase in Por-specific interleukin (IL)-4-producing CD4+ T helper lymphocytes was seen in patients with mucosal gonococcal disease and not in normal controls. Similar results were observed in CD8+ T lymphocytes from these patients. There was no measured increase in IL-2, IL-10, IL-12, interferon-gamma, or tumor necrosis factor-alpha production by T lymphocytes from infected subjects on incubation with Por. Concomitant increases in IL-4 production in T lymphocytes from infected subjects expressing the mucosal addresin VLAalpha4/beta7 on their surface were also observed on Por incubation, but the increases were similar in T lymphocytes that were VLAalpha4/beta7 negative. In conclusion, mucosal gonococcal disease can induce Por-specific circulating T lymphocytes with a Th2 phenotype, and a portion of these Por-specific T lymphocytes can potentially traffic to mucosal surfaces.