The cDNA of murine secretory leukoprotease inhibitor (SLPI) was cloned from a mouse lung cDNA library. The amino acid sequence deduced from the cDNA showed 58 and 51% homology with those of human and porcine SLPI, respectively. A two-domain structure with similar amino acid sequences, four intradomain disulfide bonds, and high proline content, which are characteristics common to human and porcine SLPI, was also found in the mouse protein. The amino acid residues for the signal sequence and active site are also conserved in mouse SLPI. RNase protection assay showed the expression of the SLPI gene in liver, intestine, spleen, and epididymis, suggesting the distribution of SLPI in tissues other than lung and seminal vesicles. In the lung infected with Streptococcus pneumoniae strain FP1284, 10 h after inoculation of bacteria the number of SLPI mRNA transcripts was three times higher than baseline. The increased level of expression remained constant for at least 48 h. This result clearly contrasts to that obtained for spleen, in which the SLPI mRNA transcript level was mostly unchanged during the course of pneumonia. These facts suggested the local regulation of the SLPI gene expression in vivo in response to inflammatory stimuli at the site of inflammation.