The modulation of histocompatibility antigens (HLA) expression by four different agents (gamma-IFN, LPS, PMA and 5-azaC) was investigated on a human tumor derived cell line that did not constitutively express HLA class I and class II molecules on its surface. Demethylating drug 5-azaC induced HLA class I but not HLA class II antigen expression. Gamma interferon and LPS induced HLA-DR and HLA-DP, but not HLA-DQ class II nor HLA class I antigens, while phorbol ester was unable to induce either class I or II molecule expression of the HLA system. These results suggest that HLA class I expression is constitutively inhibited by methylation of its coding genes. Treatment with 5-azaC leads to the HLA class I molecule expression, while HLA class II genes, DR and DP, seem to be under a different inhibitory mechanism as it was induced by LPS and gamma-interferon but not by 5-azaC. HLA-DQ class II antigens were not detected in response to any of the immunomodulators used.