T cell specificity is determined by the combinatorial association of specific variable (V), diversity (D), and junctional (J) regions. Clones of T cells (clonaliid can occur, in the blood or in tissue, after prolif-TCR (T cell receptor) p chain PCR product can also be directly sequenced, allowing simple and easy identification of Vp and CDR3 sequence from a small number of cells. The utility of this method is , I eration of activated T cells. Determining clona'lity in mutation assays is necessary to distinguish between mutants and mutational events. We have developed a novel approach to determine clonality among T cell isolates, using restriction digests of PCR-amplified cDNA of the T cell receptor p gene. The T cell receptor p gene was PCR-amplified by use of a consensus primer, beginning from a cell pellet of 2,000-5,000 cells or from extracted RNA. This demonstrated by PCR, restriction digest, and sequencing of the TCR p cDNA from eight T cell clones isolated from 2 individuals. A clone of three identical isolates (one 3-mer) and a clone of two identical isolates (one 2-mer) were determined from restriction digests using two different enzymes. This new method is an easier and more rapid way of determining clonality than traditional methods, e.g., Southern blotting.