The experiments were to determine if ectopic splenic tissue in humans would restore to normal those antibody responses which are reduced in patients who have been splenectomized. The IgM and IgG antibody response to subcutaneous injection of polyvalent pneumococcal polysaccharide vaccine (PNEUMOVAX) was determined in 34 patients who had been splenectomized for trauma and 14 controls, by measuring the concentration of antibody specific for five of the serotypes in the vaccine in serum samples taken before and 1 month after the immunization. The patients had significantly lower post-immunization concentrations of IgM antibody for three of the five serotypes measured, and IgG for two of the five. The antibody response to the immunization was assessed by comparing the post- to the pre-immunization concentration of antibody by analysis of covariance. The patients had a significantly lower IgM response to three of the five serotypes measured and IgG response to four of the five. It is concluded that in adult humans the spleen is important in the maintenance of normal humoral immune responses. The presence and degree of ectopic splenic regrowth (splenosis) in the splenectomized patients was assessed by a spleen-specific radio-isotopic scan. There was no difference between patients with splenosis and those without, or between those with different degrees of splenosis, in any of the parameters of the antibody response measured. This is in vivo evidence indicating that ectopic splenic tissue in humans does not normalize the altered antibody responses observed following splenectomy.