Immunodeficient CBA/N (xid) mice are highly susceptible to Streptococcus pneumoniae infection. Previous studies indicated that this susceptibility may be attributed to the lack of antibodies to phosphorylcholine (PC) in the circulation of these animals. We now provide direct proof that when these mice are genetically manipulated to produce significant amounts of circulating anti-PC immunoglobulin G antibodies of the T15 idiotype, they can be protected against a lethal challenge with S. pneumoniae. Transgenic mice were also used to investigate whether the transgene-encoded antibodies could protect the animals against another PC-bearing microorganism, Trichinella spiralis; in this case, there was no protection. These results were further supported by experiments with CFW mice which had been immunized to produce high levels of anti-PC antibodies but which were found to be just as susceptible to T. spiralis infection as nonimmunized animals.