The majority of T cells located in peripheral lymphoid organs are dependents on the thymus for regular differentiation and function. Only a minority of T lymphocytes are thymus-independent. These cells pass by extrathymic maturation processes and become mature T lymphocytes. Some data suggest that mechanism of extrathymic lymphocytes maturation (eTLM) includes migration, proliferation, differentiation and selection of lymphocytes as well as thymic pathway. With aging and progression of thymic involution or in accidental thymic involution, pathway of eTLM derives emphasis. T cells from extrathymic pathway probably can polarize action of thymic-dependent T cells or participate in immune reaction in antigen-destructive or antigen-protective manners. Consequently, extrathymic pathways can be a source of self-reactive T cells or cells which participate in mechanisms of trophoblast or tumor escape. Results of eTLM probably are not presets, already depend upon many factors and microenvironmental snapshots. Factors like cytokines, prostaglandine, microbes, MHC molecules, hormones, Fas ligand, heat shock proteins, phenotypes of dendritic cells and APCs, probably can be polarizing courses of eTLM pathway. Definitive to the course of extrathymic-derived cells action, presumably is resultant of microenvironmental relations and interactions of foregoing factors. Hypothesis that microbes, especially viruses, can be promoters of extrathymic (self)antigen-reactive lymphocytes maturation is real as well as hypothesis that extrathymic lymphocytes selection and products of selected lymphocytes can be included in mechanisms of tumor, trophoblast and transplant rejection or escape. (C) 2003 Elsevier Science Ltd. All rights reserved.