The expression and regulation of porcine CD44 were studied under various experimental conditions and in the context of lymphocyte differentiational and functional status. The CD44 molecule was subject to antigenic modulation by the anti-CD44 mAbs to different degrees depending on the type of cross-linking reagent and could be induced to shed from the cell surface. The reexpression of CD44 on papain-denuded lymphocytes was heterogeneous, as about half of the cells failed to resynthesize the molecule after prolonged culture, whereas the rest of the cells had a high turnover. Stimulation of lymphocytes by mitogens caused prolonged, dose-dependent elevation of the expression of CD44. Expression of CD44 on lymph node cells was found to be correlated with the expression of CD2 and sIgM. A CD2-CD4-sIgM-CD44- MHC Class II(hi)CD45+ cell subset was identified, which was present in small numbers in lymph nodes but was enriched in gut-associated lymphoid tissues. In the thymus, CD44 expression seemed to be correlated with the differentiation status of thymocyutes. In general, the expression of CD44 in the lymphoid tissues tested appeared to be related to their level of cell migration capacity. © 1993 Academic Press, Inc.