Human gingival organ culture was used to test the hypothesis that gamma interferon (gamma-IFN), which induces HLA-DR and HLA-DQ antigens on Langerhans cells, modulates CD4 antigen expression on these same cells. Before culture, the density of CD4+ cells in the gingival epithelium was 12.7% +/- 3.8% of the density of CD1+ cells. gamma-IFN (200 IU/ml) enhanced CD4 expression such that at 24 h, all CD1+ cells also expressed CD4. Prostaglandin E2, which in isolation had no effect, partially abrogated the stimulatory effect of gamma-IFN on CD4 expression. These results imply that gamma-IFN and prostaglandin E2 are two signals which regulate CD4 expression on gingival Langerhans cells.