Selective cytotoxicity of normal guinea pig serum affords a novel means for recognizing as well as functionally characterizing subsets of T lymphocytes. The phenomenon also lends itself to differential definition of cell membrane components of normal and tumoral lymphoid cells. Cytotoxicity in this system results from antibody-independent activation of the alternative complement pathway. This reaction will be exploited in this research to provide new insights into the ability of discrete lymphocyte subpopulations to undertake immunological functions in relation to expression (or lack of expression) of surface markers. The method is also suitable for studying membrane changes occurring during blastic transformation and proliferation of both normal and neoplastic lymphocytes. Experimental approaches are designed to: a) Establish the capacity of discrete subsets of Thy-1-bearing rat lymphocytes to display typical T cell functions: b) define the ontogeny, distribution and kinetics of expression of GPS reactivity by normal lymphocytes; c) discriminate, on the basis of guinea pig complement reactivity, between cell surface characteristics (markers) of normal and malignant lymphoid cells; and d) establish traffic and homing patterns of lymphocytes seeking maturation through differentiation processes. This investigation will contribute to a better understanding of the relative contributions of unique subsets of lymphocytes to the mounting of immune responses. It is also anticipated that differential properties of tumor cells will be more clearly defined by the results of these studies.