Unmethylated CpG dinucleotides within bacterial DNA or synthetic oligodeoxynucleotides (ODNs) can activate immune cells. A panel of synthetic oligodeoxynucleotides was evaluated in vitro for their ability to enhance the innate immune response of common carp (Cyprinus carpio L.). In vitro addition of CpG-ODNs enhanced the phagocytic activity and superoxide anion production of stimulated kidney phagocytes. The CpG-ODNs also induced lymphocyte proliferation in the fish kidney cells. The ODNs containing multiple CpGs generally resulted in greater stimulatory capacity, although CpGs located at the terminus of an ODN were ineffective. These results indicated that CpG-ODNs enhance the innate immune response of common carp. (C) 2003 Elsevier Science B.V. All rights reserved.