A monoclonal antibody to human glomerular type IV collagen has been characterized and used in an immunohistochemical study of the distribution of this basement membrane protein in dysplasias, intraepithelial carcinomas, and infiltrating squamous cell carcinomas. Four squamous carcinoma cell lines established as xenografts in nude mice were also examined. In normal epidermis and mucosae, the basement membrane was clearly defined and intact. In areas of intraepidermal carcinoma, the basal lamina as defined by the antibody was usually continuous, and defects were only present in areas associated with an inflammatory infiltrate. Invasive squamous cell carcinomas, regardless of the degree of differentiation had a clearly delineated basement membrane at the epithelial stromal interphase. In areas of invasion, far removed from the in situ component, there were protrusions of tumor cells through the basement membrane into the stroma. Other abnormalities of basement membrane production such as aggregation of basement membrane and reduplication of the basal lamina were also associated with the carcinomas. There was a similar distribution of basal lamina material in involved lymph nodes and in squamous cell carcinomas that were growing as xenografts in nude mice. Our studies suggest that the loss of basement membrane type IV collagen is not generally associated with invasive squamous cell carcinomas and is not likely to be useful in the assessment of early invasion in this tumor. The similar distribution of type IV collagen in the xenografts and in the infiltrating tumors suggests that this system, in conjunction with the use of the same cell lines in vitro, will provide a model with which to study the control of deposition of type IV collagen.