We established conditions for inducing antigen-specific tolerance in T_h2 lymphocytes by means of oral tolerance. Mice were continuously exposed to ovalbumin in their drinking water for a minimal period of 20 days and then immunized against antigen in either complete Freund's adjuvant or Al(OH)₃. This feeding regimen tolerized both T_h2 and T_h1 responses as shown by diminished proliferation, cytokine secretion (IL-4, IL-2 and IFN-γ) and specific cytokine mRNA expression (IL-4, IL-2 and IFN-γ) in vitro, as well as by absence of specific antibody production (lgG1, lgG2a, gG2b and IgE) in vivo. Conditions for generating T_h2 lymphocyte tolerance were different from those required to generate tolerance in T_h1 lymphocytes: these included extended, continuous exposure to high dosages of antigen, rather than a single or intermittent feeding regimen which was sufficient to induce tolerance in T_h1 lymphocytes. These findings suggest that continuous oral exposure to a tolerogen may be a biologically relevant strategy to tolerize both T_h1- and T_h-dependent responses, and extend the potential clinical use of oral tolerance to ailments mediated by T_h2 lymphocytes.