Two sisters with clinical elements of mixed connective tissue disease were found to have anti-nuclear RNP (nRNP) antibodies. These antibodies were not found in the six other family members examined. The sisters had inherited an identical HLA haplotype A2-Bw61-Cw3-DR1 from their mother who had had Raynaud's phenomenon for several years. Analysis of peripheral lymphocyte subsets in the patients and their immediate relatives showed decreased OKT-4-positive cells in one of the patients and increased OKT-8-positive cells in both patients, their father and their brother, resulting in lower OKT 4/OKT 8 ratios in these members of the family. This is the third description of the familial occurrence of anti-nRNP antibodies and it adds further evidence for the implication of genetic factors in the development of anti-nRNP antibodies.