Background: Inhaled corticosteroids, such as budesonide, attenuate the inflammatory response in asthma. However, patient noncompliance and side effects of available inhaled corticosteroids limit their use. Liposomes are currently used in medicine to deliver a variety of drugs. Objective: The objective of our study was to determine whether weekly therapy with budesonide encapsulated in sterically stabilized (stealth) liposomes would be comparable to daily budesonide therapy in reducing allergic inflammation. Methods: Ovalbumin-sensitized C57/Black 6 mice received aerosolized (1) budesonide encapsulated in stealth or conventional liposomes, administered weekly, (2) budesonide (without liposomes), administered either daily or weekly, or (3) empty stealth liposomes, administered weekly. All treatment groups were compared with sensitized untreated or unsensitized mice. Histopathologic examination of the lung tissues and measurements of eosinophil peroxidase activity, peripheral blood eosinophil counts, and total serum IgE levels were done weekly for 4 weeks. Results: Weekly therapy with budesonide encapsulated in stealth liposomes was as effective as daily budesonide therapy in decreasing lung inflammation and lowering eosinophil peroxidase activity, peripheral blood eosinophils, and total serum IgE levels. In none of the other groups was there a significant decrease in the inflammatory parameters evaluated. Conclusion: We conclude that weekly therapy with budesonide encapsulated in stealth liposomes is as effective as daily budesonide in reducing markers of lung inflammation in experimental asthma. This novel strategy offers an effective alternative to standard daily budesonide therapy in asthma and has the potential to reduce toxicity and improve compliance. (J Allergy Clin Immunol 2003;111:321-7.)