The aim of the present study was to evaluate the influence of Kupffer cell phagocytosis blockade (KCPB) on the production of reaginic (IgE) and non-reaginic (IgG1) ovalbumin antibodies in an experimental animal model. Forty-two female heterozygous Gunn rats were injected with two 100 micrograms doses of ovalbumin separated by 13 days, into jugular vein (Group I, n = 10), portal vein (Group II, n = 10), jugular vein with prior KCPB (Group III, n = 10) and portal vein with prior KCPB (Group IV, n = 12). KCPB was induced with gadolinium chloride (5 mg/kg body weight, 24 hr before each ovalbumin administration). Antibodies were determined by passive cutaneous anaphylaxis in sera obtained 12 days after the first dose of ovalbumin and 8 days after the second one. No antibodies were detected at any time in Group II. The maximum response was observed in Group IV in which, after two doses of ovalbumin, 100% of the animals presented IgG1 and 58% presented detectable IgE antibodies. Differences between group IV and the other groups were statistically significant. This phenomenon does not seem to be due to a systemic effect of gadolinium chloride since humoral response was not increased in Group III with respect to Group I. It is concluded that the liver represents a barrier to IgE and IgG1 sensitization. KCPB not only eliminates this barrier, but also clearly increases antibody production to a protein antigen (ovalbumin) arriving at the liver through the portal vein.