We have expressed active human cathepsin S to 60 mg/L in Sf9 cells using a baculovirus system. Production of milligram quantities has facilitated crystallographic studies to determine the structure of this enzyme, which has unique properties among lysosomal cysteine proteinases. Recombinant, irreversibly inhibited cathepsin S was crystallized from ammonium phosphate at 17 °C. The crystals diffract to at least 2.3 Å, and belong to the orthorhombic crystal system with a primitive lattice. Approximate cell dimensions are: a = 37.7 Å, b = 73.9 Å, and c = 106.7 Å. There is most likely one molecule per asymmetric unit.