Antigen challenge has profound effects on a regional lymph node (LN); it leads to an increase in blood flow to the node, and a marked increase in lymphocyte output through the efferent lymphatics. We used the isolated LN model developed in the sheep to see if antigen challenge in a LN resembled inflammation in peripheral tissues. Following stimulation with an antigen (purified protein derivative of tuberculin), lymphocyte output from the LN showed the typical periods of “lymphocyte shutdown” and “recruitment”. The shutdown phase, when cell numbers in efferent lymph dropped by ∼80%, affected almost exclusively the naive‐type (adhesion10, L‐selectin+) T cell population. The large increase in T cell traffic through the node during the recuitment phase was mostly due to CD4+ memory‐type T cells and, moreover, the majority of these T cells were L‐selectin−, indicating that these cells were crossing from the blood by a molecular mechanism other than L‐selectin interaction with its ligand, the “lymph node vascular addressin” (MECA‐79). Examination of LN high endothelial venules revealed the presence of vascular cell adhesion molecule‐1 (VCAM‐1), an endothelial adhesion molecule which has been reported to bind preferentially memory‐type T cells in inflammatory lesions. Within the skin, antigen challenge also induced the rapid expression of VCAM‐1 on vascular endothelium. It was purely memory‐type T cells (β1−, L‐selectin+/−) that collected in lymph draining from this tissue. However within chronically inflamed skin, the MECA‐79 determinant appeared on vascular endothelium, and a small proportion of T cells draining from chronically inflamed skin were of naive‐type. The present results illustrate that there are similarities in the cellular and molecular events that characterize antigen stimulation of a LN and inflammation in a peripheral tissue.