Cystatin A is the major cysteine proteinase inhibitor in human squamous epithelia. We investigated the occurrence of cystatin A in normal, condylomatous, and dysplastic lesions of the cervix with or without human papillomavirus (HPV) infection. Cystatin A was detected by immunohistochemistry and HPV infection by DNA hybridization techniques. In the normal uterine cervix, cystatin A was seen throughout the epithelium, except in the basal and parabasal cell layers. In condylomatous lesions, the staining intensity was similar to that in normal epithelium. In low-grade cervical intraepithelial neoplasias (CINs), reduced staining was seen in the lower third of the epithelium; in high-grade CINs, a reduction in staining intensity was also seen in the middle and upper thirds. Cystatin A staining in epithelia and nuclei was negative in highly cellular and poorly differentiated CIN III. The cytoplasmic staining of cystatin A did not correlate with presence or type of HPV DNA. In the high-grade CINs infected with HPV types 16 and 18, however, cystatin A staining was more often confined to the nuclear compartment.