Squamous cell carcinoma antigen (SCC antigen) is a member of serine protease inhibitor's family, and appears in the differentiated types of malignant and nonmalignant squamous cells. This study shows the effects of calcium on the production of SCC antigen in normal human keratinocytes. The keratinocytes were treated with calcium with final concentration of 0.15, 0.5, 1.0 and 2.0mM for up to 5 days. mRNA expression and cytoplasmic contents of SCC antigen were significantly increased by 0.5 and 1.0mM calcium, but the release of SCC antigen into the medium rather decreased as the calcium concentrations were increased, showing the different behaviors in the production and release of SCC antigen. The immunohistochemical studies using a specific monoclonal antibody against SCC antigen also demonstrated that the intensity of staining was increased significantly in the calcium treated keratinocytes. These results indicated that calcium would influence the production and release of SCC antigen in keratinocyte, which should be involved in the proliferation and the differentiation of keratinocyte.