The active N-terminal domain of the mouse tissue inhibitor of metalloproteinases-1 is a 14.1-kDa polypeptide with three disulfide bonds. When expressed using a T7 system inEscherichia coli,this truncated protein, in contrast to the WT protein, was found only in trace amounts in the cell. However, when the coding sequence was placed downstream of a 60-bp sequence that encoded an in-frame histidine-rich “tag,” the fusion product (NF.TIMP*His) was expressed in considerably increased abundance. WT.TIMP-1 was expressed in abundance with or without the tag. The mRNAs encoding the various forms of TIMP were present in similar amounts in all four cases. NF.TIMP*His, renatured and purified on a nickel affinity column, was found to be about 10-fold less effective than native human TIMP-2 at inhibiting cleavage of collagen type I by human fibroblast collagenase. A thrombin cleavage site in the tag was susceptible to cleavage by low levels of a contaminating proteinase.