The T cell hybridization technique can be used to prepare continuous cell lines which express the antigen specificity and function of T cells within the milieu of a proliferating lymphoma. Technical details for the preparation and maintenance, selection and analysis of T cell hybrids are defined. Techniques for cloning of hybrid cells and production of hybrid-derived tumors are also presented. Parameters influencing the hybridization frequency and the production of functional hybrids are discussed. A variety of T cell subsets, including suppressor cells and delayed-type hypersensitivity effector cells as well as T cells maintained on TCGF, are excellent sources of primary parents for hybridization. When BW 5147 is used as the T lymphomas parent in these experiments, the resulting hybridization frequencies range between 10 and 434 X 10(-7). We have had moderate success using YAC-1; however, additional lines such as L5178Y, BALENTL 5, EL4 BU and S491TB.2 have proved ineffective as sources of T lymphoma parents. The technique of T cell hybridization is evaluation in terms of retention of differentiated functions and the stability and growth characteristics of the resultant hybrids.