The invention provides immunostimulatory oligonucleotides having at least one CpG dinucleotide and a secondary structure at the 5′- or 3′-end. These oligonucleotides have either reduced or improved immunostimulatory properties. The invention establishes that 5′-terminal secondary structures affect immunostimulatory activity significantly more than those at the 3′-end. The invention also provides methods for increasing or decreasing the immunostimulatory activity of a CpG-containing nucleic acid.