The results of studies to evaluate the possible importance of serratia proteases in the development of experimental Serratia marcescens pneumonia revealed the following. (i) Administration of a highly purified serratia protease to the lungs of guinea pigs and mice resulted in extensive pulmonary edema and hemorrhage similar to that observed in animals having an experimentally induced, acute serratia pneumonia. (ii) Guinea pigs subcutaneously vaccinated with the protease developed low levels of antiprotease antibodies and were partially protected against serratia pneumonia, as demonstrated by a significant increase in survival time. Mice intranasally vaccinated with the protease also developed antiprotease antibodies and were protected against serratia pneumonia, as demonstrated by a significant increase in survival time and an increase in the number of survivors. (iii) Serratia protease was detected in lung tissue extracts prepared from the lungs of guinea pigs dying of serratia pneumonia. Our findings support the idea that serratia protease(s) is involved in the pathogenesis of experimental serratia pneumonia.