Immunization of mice with membranes from a virus-transformed human keratinocyte cell line (KJD-I/SV40) yielded an IgM monoclonal antibody (MAb 3H-I) which reacted with the membrane and cytoplasm of KJD-I/SV40 cells and in the perinuclear region of a squamous-cell carcinoma line (Colo-16). Immunohistochemistry of formalin-fixed, paraffin-embedded sections using MAb 3H-I gave intense staining of proliferating squamous epithelium in several characteristic patterns. Acanthotic squamous epithelium and well-differentiated squamous-cell carcinomas (SCC) demonstrated a membranous staining pattern whereas psoriatic skin and undifferentiated SCC of the head and neck exhibited diffuse cytoplasmic, focal cytoplasmic or, in some tumours, no staining. Simple squamous epithelium was unreactive. Western blotting revealed an antigen of 55 kDa. The epitope recognized by MAb 3H-I may be a marker for particular stages of squamous proliferation and differentiation.