Some humans are persistently more susceptible to gastrointestinal nematodes than others. Here, for the first time, susceptibility to reinfection has been linked to host cytokine responses. Ascaris lumbricoides and Trichuris trichiura abundance was assessed immediately before and 8–9 months after deworming in a Cameroonian population (starting n = 191). Profiles of whole-blood cytokine responses to parasite antigens (for interleukin [IL]-5, IL-13, IL-10, IL-12p40, tumor necrosis factor-α, and interferon-γ), assayed before treatment, were significantly related both to an overall measure of host susceptibility and to susceptibility to reinfection. Significant effects were primarily due to a negative association between IL-13 and IL-5 responses and infection. Persistently susceptible individuals were, therefore, characterized by a weak T helper cell type 2 response. The apparent plasticity of age-specific cytokine response-worm abundance relationships between different populations is also discussed.