The murine model of ovalbumin (OVA)-induced allergy was used to evaluate the effectiveness of oral treatment with the leaf extract of Cissampelos sympodialis Eichl. (Menispermaceae) (CS) in the modulation of immunoglobulin E (IgE) production and T cell activation. CS treatment with doses ranging from 200 to 600 mg/Kg/day for 15 days before and during OVA-sensitization promoted reduction in total and OVA-specific serum IgE. CS at 400 or 600 mg/Kg/day also reduced paw edema induced by local OVA challenge. Daily intake of up to 600 mg/Kg of oral CS by BALB/c mice did not reduce weight gain, which is indicative of a lack of systemic toxicity. To assess the effect of CS treatment on T cell proliferative response to stimuli in vitro, the mitogenic response of spleen cells of treated and control animals were evaluated. Cells from CS-treated animals showed an elevated background proliferative response to concanavalin-A (Con-A) when compared to those from control animals. Oral intake of CS increased the in vitro production of IFN-gamma and IL-10 by Con-A stimulated cells. Mice treated with 200 mg/Kg/day CS showed increasing levels of IFN-gamma. These results show that oral treatment with Cissampelos sympodialis extract has an immunomodulatory effect, reducing allergy-associated responses possibly by a preferential activation of Th1-type cytokines.