The recent increase in the prevalence of and mortality from asthma has inspired several new molecular techniques to improve treatment. Because asthma is a disease of gene polymorphism, gene therapy is unlikely to be effective. Alternative methods use oligonucleotides (ODNs) in the form of (1) DNA vaccination expressing CpG motifs that mimic bacterial DNA or (2) antisense ODNs inhaled and locally deposited into pulmonary airways to specifically modulate receptors for inflammatory mediators. DNA vaccination, a form of "molecular immune surveillance," attenuates a TH2 predominance. Antisense directed against the adenosine A(1 ) receptor abrogates A(1 ) sensitivity, improves allergen-induced immediate airway obstruction, and inhibits the expected increase in histamine responsiveness in allergic rabbits. Adenosine receptor inhibition lasts for an average of 7 days and the majority of the antisense remains in the lung. ODN therapy for asthma seem unlimited, but confirmation awaits the extension from animal models to human studies.