A cDNA clone which expresses a protein that cross-reacts immunologically with the human C1 and C2 hnRNP core proteins has been isolated. The clone was selected by a sensitive immunochemical assay employing an avidin-biotin complex for detection, and identified as a clone for the hnRNP C proteins by a highly sensitive antibody select assay that is described here. The clone contains 677 nucleotides, and, as shown by northern blotting, is derived from a 1.5 Kb poly(A)+ mRNA. There are regions of strong homology between the human and mouse genes, weak homology is seen with chicken DNA, and very little, if any, homology can be detected with Drosophila, Artemia, sea urchin, or yeast DNAs. Two peptides (a total of 24 amino acids) of the calf thymus single-stranded DNA binding protein UP2 show perfect homology with the deduced amino acid sequence of the clone, suggesting that UP2 is related to the hnRNP C proteins. There is also a region that has a sequence very similar to two regions of the single-stranded DNA binding protein UP1 that contain proposed DNA binding sites.