The leukocyte common antigen (LCA, CD45) of humans and rodents is expressed exclusively by leukocytes, and has been implicated in a number of immune functions (1-4), although its precise function is still unknown. Three monoclonal antibodies (mAbs) were produced which identified different epitopes on the LCA of sheep. mAbs 1-11-32 and 38-42 reacted with determinants of LCA expressed on all leukocytes, but showed differential reactivity with thymocytes. Another antibody, 20-96, identified an epitope of LCA expressed mainly on B cells, but also on a unique lymphocyte subset contained mostly in peripheral blood, which was 20-96high, sIg-, CD4-, CD8-, SBU-T19-, but CD5+. These cells constituted only 5-6% of PBL. The cellular lineage of this latter subset is uncertain since these cells appeared to be unrelated to B cells, And were absent from the thymus. Unlike the other two mAbs to LCA, 20-96 was not reactive with macrophages and granulocytes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of material immunoprecipitated by the "pan" LCA-specific mAbs revealed lymphocyte forms with molecular weights (MW) of 220, 210, and 190K, whereas 20-96 immunoprecipitated only a 220K MW form. The expression and MW of LCA on thymocytes or ileal Peyer's patch (IPP) cells differed from those on peripheral lymphocytes. B cells in IPP, which constitute 98% of cells, expressed the 20-96 determinant at low density, in contrast to its high expression on peripheral B cells. LCA from IPP existed in two forms of 220 and 190K MW, whereas LCA from peripheral B cells was entirely 220K MW, and thymus 210 and 190K MW.