To understand the integrin requirements of T-helper (TH) effector subsets, we investigated the contribution of CD18 (β2 integrin) to TH1 and TH2 function in vitro and in relevant disease models. CD18-deficient (Itgb2) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2 mice were better able to resolve Leishmania major infection and generated a superior TH1 immune response, as assessed from draining lymph nodes. In contrast, TH2-dependent allergic lung disease was markedly impaired in mutant mice. In both models, development of TH1 and TH2 cells in spleens was normal, but accumulation of T H2 (not TH1) cells at inflammatory sites was reduced. Thus, CD18 is selectively required for TH2, but not TH1, homing and has a minimal influence on T-effector development. These findings suggest a new integrin-based therapeutic approach in which the outcomes of diverse diseases may be favorably influenced by altering the homing of T H2 cells.