SummaryAn interleukin 4 (Ib4)-specific monoclonal antibody (mAb) was administered to mice infected systemically with the yeast Candida albicans, and the animals were monitored for mortality, development of delayed-type hypersensitivity, production of antibodies of different isotypes, release of II.-2, II.-4, Ib6, and interferon 3' (IFN-3') in vitro by splenic CD4 + lymphocytes, and levels of Ib4 and IFN-3' mRNA in these cells. Neutralization of IL-4 by three weekly injections of mAb in several independent experiments resulted in an overall cure rate of 81% versus 0% of controls. Cure was associated with efficient clearance of the yeast from infected organs and histologic evidence of disease resolution, detection of strong T helper type 1 (Thl) responses, and establishment of long-lasting protective immunity. Soon after infection, and as a result of the first or second injection of mAb, there was a decrease in Ib4 mRNA in CD4 + cells, which was accompanied by an increase in the levels of IFN-3'-specific transcripts. Our data thus indicate