Transgenic mice overexpressing human neuroserpin with the S52R-Portland mutation under the control of the mouse Thy1 promoter were generated by pronuclear injection into fertilized oocytes using an expression cassette derived from the murine Thy1 gene. The S52R-Portland mutation was introduced into the human neuroserpin cDNA using the polymerase chain reaction technique. The transgene was expressed in central nervous system neurons throughout postnatal life. The expression levels for transgenic mice with human Portland neuroserpin is 3.3 times [line Tg(NSS52R)794Zbz] above the endogenous neuroserpin level of wild-type mice. (J:120135)