In an attempt to develop an assay specific for antibody to capsular polysaccharide (PS) of Streptococcus pneumoniae, the ability of ELISA and Farr (radioactive antigen-binding) assay for antibodies to 6B and 19A PS to be affected by antibodies to C-polysaccharide (C-PS) was compared. Preabsorption with C-PS reduced values obtained by ELISA for anti-6B antibody by > 3-fold in 5 of 10 preimmune and 7 of 26 postimmune sera. In contrast, absorption reduced values by > 3-fold in 0 of 36 samples studied with the Farr assay. Similar results were observed when the absorption was done with CSR-SCS2 S. pneumoniae. Furthermore, when anti-19A antibody levels were examined, preabsorption with R36a S. pneumoniae reduced ELISA values by 3-fold in 7 of 22 samples, whereas no samples had 3-fold reduction by Farr assay. Thus, the Farr assay for capsular PS is less affected than the ELISA by anti-C-PS antibody.