The aim of this study was to investigate interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by peripheral blood mononuclear cells (PBMC) in response to oral challenge in patients with food allergy. Thirty-one patients were compared with 10 healthy subjects. Cell cultures were prepared before and 150 min after single-blind, placebo-controlled, oral food challenge. In vitro production of cytokines was observed after stimulation with phytohemagglutinin (PHA) plus phorbol myristate acetate (PMA). Patients were characterized according to their reactions. In vitro IL-4 production was significantly greater in patients with food sensitization than in controls. The 18 patients with positive food challenge presented significantly greater IL-4 production after food challenge than before. IFN-gamma production was not modified. In the 10 control subjects and in 13 patients with negative food challenge, IL-4 and IFN-gamma production was comparable before and after food challenge. The increased IL-4 production in patients with positive oral food challenge could account for the development of polysensitization. This situation might be relevant to other allergic diseases and to treatments.