We synthesized and cloned cDNA from human peripheral blood mononuclear cell (PBMC) transcripts that were hybrid selected by pCRP5, a liver C-reactive protein (CRP)-specific cDNA (Woo, P.,J.R. Korenberg, and A.S. Whitehead. 1985. J.Biol. Chem. 260:13384). Three hybrid-selected cDNA clones, HScDNA1, HScDNA3, and HScDNA8, were isolated and characterized. Nucleotide sequence analysis of the 5' end of the smaller clones, HScDNA1 and HScDNA8, demonstrated that these two PBMC clones are homologous to the 3' and 5' ends, respectively, of pCRP5. Our largest clone, HScDNA3, is larger than pCRP5, extending beyond both the 5' and 3' limits of pCRP5. Therefore, HScDNA3 was coded by human PBMC and not by the hybrid selection vehicle, pCRP5. HScDNA3 lacks the intervening sequence verifying that this clone is DNA made from a PBMC mRNA and not genomic DNA. The complete nucleotide sequence revealed that HScDNA3 is greater than 99% homologous to the CRP gene. These results demonstrate that PBMC express the CRP gene. Based on our previous report, which shows that peripheral blood cells synthesize a peptide recognized by anti-CRP (Kuta, A.E., and L.L. Baum. 1986. J. Exp. Med. 164:321), in conjunction with the data presented here, we conclude that human PBMC can synthesize CRP.