Monoclonal antibodies against pneumococcal surface protein A (PspA) have been shown to protect mice from fatal pneumococcal infection. PspA is highly variable serologically, raising the possibility that pA from one strain might not be able to elicit protective responses against strains which possess serologically different PspA. We have prepared a λgt11 library of pneumococcal genomic DNA and identified a clone expressing PspA. The recombinant PspA in this phage lysate elicited protection against pneumococcal infections with three strains of two different capsular serotypes. This finding demonstrated that PspA could elicit a protective response in the absence of other pneumococcal antigens. The observed protection was probably antibody mediated because it could be passively transferred with immune sera. Lambda lysates producing pneumococcal proteins other than PspA failed to elicit protection against fatal pneumococcal infection.