The oxygen permeation resistance of highly condensed monolayers composed of a homologous series of saturated diacyl phosphatidylcholine lipids was measured using a novel technique that combined micromanipulation and electrochemical techniques. The use of lipid monolayer-coated air microbubbles allowed measurement of the oxygen permeation resistance of fully condensed lipid monolayers that were previously unavailable using classical film balance techniques. Fully condensed lipid monolayers were found to significantly impede oxygen transport from the gas core, an effect that increased with lipid acyl chain length. The magnitudes of the measured oxygen permeation resistances, 10(2) to 10(3) s/cm, agree with literature values for various gases permeating through highly condensed fatty acid and alcohol monolayers. Such high resistances can account for the previously observed hindered dissolution of lipid-stabilized microbubbles in degassed media. Additionally, the ability to probe a lipid monolayer in its fully condensed state leads to new physical insights into monolayer permeation.