We show that the Th/To ribonucleoprotein is defined by (i) the co-immunoprecipitation of two RNAs, (ii) the co-immunoprecipitation of four major polypeptides and (iii) the quantitative immune recognition of both RNase P and RNase MRP. No serum was found that recognizes either one of these two enzymes exclusively. The specific co-immunoprecipitation of RNase MRP and RNase P by all Th/To ribonucleoprotein autoantibodies indicates that the anti-Th/To autoimmune response is directed against both enzymes in a quantitatively indistinguishable manner. Thus the Th/To ribonucleoprotein is defined by RNase P and RNase MRP.