The distribution of antigen-specific memory T cells in different lymph nodes of sheep was determined using an antigen-specific in vitro proliferation assay. Lymph nodes were collected from sheep immunized simultaneously with avidin or ovalbumin in a peripheral tissue site (hind leg muscle) and keyhole limpet haemocyanin (KLH) in an intestinal tissue site (gut wall or colonic mucosa). The results showed a consistently high proliferative response in typical peripheral lymph nodes (popliteal and prescapular) and a low or negative response in gastrointestinal lymph nodes (abomasal and jejunal) while the response in other nodes was variable. The low proliferative response in the gastrointestinal lymph nodes was not due to the presence of suppressor CD8- lymphocytes and the proliferative response could not be raised to peripheral lymph nodes levels with the addition to cultures of IL-2 or mitomycin-C treated peripheral lymph node cells. The high proliferative response in the peripheral lymph nodes was not suppressed by the addition of mitomycin-C-treated gastric lymph node cells but was dramatically reduced by the addition of mAb against the IL-2-receptor or by depletion of CD4- T cells. The results suggest that antigen-specific proliferative memory T cells, which may be Th1-like memory cells, preferentially migrate to peripheral lymph nodes independent of their site of induction.