Intestinal intraepithelial lymphocytes (IEL) were studied, after isolation in humans for their surface antigens with a large variety of monoclonal antibodies. They show peculiar characteristics when compared with peripheral blood lymphocytes and intestinal laminapropria lymphocytes. Although a majority of human intraepithelial lymphocytes (IEL) express an α/β type of T cell receptor (TcR), 13% express a γ/δTcR, a percentage which was significantly higher than that found in blood and in lamina propria. In contrast to observations in mice, there was no evidence that normal human TcR γ/δ+ intestinal IEL might use preferential variable segments of γ genes. About 10% of human intestinal IEL expressed the α chain but not the β chain of CD8, thus resembling a subset of CD8 α+β− IEL, which was recently described in mice and found to be of thymoinde‐pendent origin. In addition, 10% of human IEL had a unique phenotype of immature T cells, as they bore only CD7, but no other T cell or natural killer cell markers. Finally, even the major population of IEL which expressed the usual markers of the T cell lineage (CD3,TcR α/β, CD2, CD4 or CD8 α/β) differed from peripheral blood T lymphocytes by their peculiar expression of surface antigens associated with activation. Indeed, 80% of IEL were CD45R0+, CD45A−, but co‐expression of CD11a, CD29 and LFA‐3 was inconstant. In addition, 90% of IEL expressed HML‐1. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim