Development and sequence of lymphocytes reactive to viral antigen in Peyer's patches, mesenteric lymph nodes, spleen, and peripheral blood of pigs orally inoculated with transmissible gastroenteritis virus were investigated by a lymphocyte proliferative assay. Lymphocytes reactive to the viral antigen were first detected in all the tissues of pigs tested on postinoculation day 7. Thereafter, they increased in proliferative reactivity and reached a maximal amount on postinoculation days 10 to 14. Antigen-reactive cells were persistently demonstrated in Peyer's patches and mesenteric lymph nodes for at least 110 days after inoculation, although lymphocytes decreased a little in reactivity to the viral antigen with the lapse of time. On the other hand, splenic and peripheral blood cells were found to have only transient proliferative reactivity. No antigen-reactive cells were detected in spleen or peripheral blood after postinoculation days 20 to 30. Lymphocytes decreased remarkably in reactivity to the viral antigen and phytohemagglutinin when treated with anti-porcine thymocyte serum and complement. Their reactivity to lipopolysaccharides was hardly affected by the treatment. Cells harvested on postinoculation days 45 to 60, however, responded a little to the viral antigen even after they were treated with anti-porcine thymocyte serum and complement. Lymphocytes reactive to the viral antigen and phytohemagglutinin belonged mainly to the erythrocyte rosette-forming cell fraction, whereas those reactive to lipopolysaccharides were mostly found in the rosette-nonforming cell fraction.