Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity. For example, type 1 and type 2 helper (T_H1 and T_H2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can stimulate interleukin-4 production and its overexpression is associated with defects in cell-mediated immunity, indicating that it might be involved in T_H2 polarization. Here we show that MCP-1-deficient mice are unable to mount T_H2 responses. Lymph node cells from immunized MCP-1^-/- mice synthesize extremely low levels of interleukin-4, interleukin-5 and interleukin-10, but normal amounts of interferon-γ and interleukin-2. Consequently, these mice do not accomplish the immunoglobulin subclass switch that is characteristic of T_H2 responses and are resistant to Leishmania major. These effects are direct rather than due to abnormal cell migration, because the trafficking of naive T cells is undisturbed in MCP-1^-/- mice despite the presence of MCP-1-expressing cells in secondary lymphoid organs of wild-type mice. Thus, MCP-1 influences both innate immunity, through effects on monocytes, and adaptive immunity, through control of T helper cell polarization.