The pathways of human anti-pig T cell xenorecognition have been investigated. Freshly isolated porcine alveolar lavage (AL) cells induced primary proliferative responses by human peripheral and cord blood mononuclear cells which were inhibited by anti-HLA-DR antibody (indirect xenorecognition). Following over-night culture, the AL cells acquired the capacity to stimulate proliferation by purified human T cells which was inhibited by anti-SLA-DR antibody (direct xenorecognition). The marked increase in immunogenicity in the porcine AL cells was accompanied by a phenotypic change consistent with dendritic cell maturation. Limiting dilution assays indicate that the total anti-pig T cell response, in particular that mediated by indirect xenorecognition, is stronger than comparable alloresponses.