Under most experimental circumstances, mice fed a protein antigen prod
uce a smaller serum antibody response than the response elicited in mi
ce that are parenterally immunized with that same antigen. In our expe
riments, mice fed keyhole Limpet hemocyanin or herpes simplex virus ty
pe 1 had low, if any, serum IgG antibody responses regardless of wheth
er antigen consumption was voluntary (in drinking fluids) or involunta
ry (force-fed by pipette). However, when force-feeding occurred during
CO2 anesthesia, mice produced significantly higher serum antibody res
ponses, which were comparable to those elicited in mice injected intra
peritoneally with the same antigen. Although its mechanism of action i
s unclear, this potentiating effect does not appear to be mediated by
possible CO2 mediated entry of the antigens into the respiratory tract
, since mice fed antigen immediately before CO2 anesthesia also had a
substantial antibody response.