Lysosomal/phagosomal membranes of mammalian cells are coated by highly conserved glycoproteins (lamps) that are thought to protect the membranes from degradation. Interestingly, we identified an amino acid sequence in human lamp-1 characteristic of a cleavage site for the Neisseria gonorrhoeae IgA1 protease. Furthermore, gonococci are detected in h-lamp-1-positive vacuoles after their uptake by professional phagocytes and epithelial cells. Here we demonstrate cleavage of glycosylated h-lamp-1 by the secreted gonococcal IgA1 protease. The cleavage was observed with h-lamp-1 purified from epithelial cells but not from professional phagocytes. The biological role of lamp-1 cleavage by the gonococcal protease is discussed.