Previous studies have demonstrated that monoclonal IgG and IgM antibodies to phosphocholine (PC), a determinant in the cell wall of Streptococcus pneumoniae, can protect mice from fatal infection with S. pneumoniae. In this study we demonstrate that both passive and naturally occurring anti-PC antibodies promote the clearance of S. pneumoniae from the blood. The bulk of the cleared pneumococci are apparently killed, because they fail to accumulate in reticuloendothelial tissues. These findings suggest that their protective effect is probably dependent on their ability to promote phagocytosis. We have found that on a weight basis IgG antibody is more effective at promoting blood clearance than IgM antibody. This observation fits with our earlier findings that IgG anti-PC antibody is more protective against i.v. infection than IgM anti-PC antibody. We have also demonstrated that anti-PC antibodies are protective against S. pneumoniae infection when given as late as 24 hr postinfection. This finding makes it unlikely that the ability to protect against pneumococcal infection with anti-PC antibody is dependent on an artifact associated with either their in vitro growth or the harvesting procedure.