The immune response to cholera toxin B subunit given orally was studied in 13 human volunteers. A serum IgG and IgA antitoxin response was observed, which was boosted by a second immunization. Using an immunospot assay, cells spontaneously secreting anti‐toxin IgG and IgA, but not IgM appeared transiently in the blood after immunization. There were 105 IgG‐ and 87 IgA‐secreting cells per 2 × 106 mononuclear cells 7 days after the first immunization, and 282 IgG‐ and 413 IgA‐secreting cells 5 days after the second immunization. A polyclonal increase in total IgM‐secreting cells was observed. Few anti‐toxinsecreting cells were observed in the bone marrow at the peak of the circulating cell response, which could be accounted for by contamination of the sample with peripheral blood, suggesting that the bone marrow is not a significant site of anti‐toxin‐secreting cells after oral immunization.