A sequential change in the number of circulating immunoglobulin (Ig) secreting cells of each Ig class following blood transfusion was studied using a reverse hemolytic plaque assay. The subjects studied were in two main groups, immunologically normal individuals and patients with malignant lymphoma or multiple myeloma who are, presumably, immune incompetent. A consistent increase in circulating IgG-secreting cells, along with either an earlier or simultaneous increase in IgM-secreting cells, was observed following blood transfusion in the immunologically normal individuals. An increase in IgA-secreting cells was also observed, but at a minimal magnitude. Such an increase was not apparent in patients with lymphoma or myeloma. The possible use of blood transfusion as a means of “challenging and checking” for the state of immune responsiveness in vivo is discussed.