To improve diagnostic options for pneumococcal pneumonia, an ELISA system was developed that can detect ⩽6 ng/ml capsular polysaccharide in serum. The test waslimited to 39 serotypes causing >95% of pneumococcal infections. In clinical evaluation the test identified 14 of 15 cases (missing one serotype not included). No false-positive reaction occurred. However, the duration and level of antigenemia were variable (⩾500-2.5 ng/ml) and seemed not to depend solely on the severity of infection. Therefore, the question of whether the extent of antigenemia was determined by a serotype-dependent variation in the elimination rates of polysaccharides was investigated. Clearance rates for 12 serotypes varied in rabbits and rats by a factor of >250. This remarkable variability appeared to affect the extent of clinical antigenemia. Thus, only very sensitive systems can detect circulating antigen from rapidly cleared polysaccharide serotypes. Furthermore, the question arises whether slow polysaccharide clearance contributes to the virulence of some pneumococcal serotype