The in vitro human T cell xenoresponse to porcine stimulators has been examined in detail. Alveolar lavage cells (AL cells), derived from washouts of porcine lungs were found to possess phenotypic and functional properties of porcine dendritic cells, Using AL cells that had been allowed to mature during overnight incubation, we have shown that the ''direct'' T cell xenoresponse is mediated predominantly by CD4(+) T cells that recognize SLA-DR molecules, Limiting dilution analysis assays indicate a high precursor frequency of such cells in the peripheral blood of human responders, However, in a formal comparison with direct alloresponses, the proliferative response of human T cells to porcine dendritic cells was found to be significantly weaker, Using HLA-DR and SLA-DR-transfected murine and porcine cell lines, we have shown that this relative weakness is due in part to an inefficiency of cognate interactions. In contrast, the noncognate interactions between human T cells and porcine stimulators are as efficient as those with human APC.