We report that certain oligonucleotides are capable of inhibiting cell surface induction of the major histocompatibility complex class I (MHC-I) proteins by interferon-γ in K562 cells. The inhibition by oligodeoxynucleotide 15' GGG GTT GGT TGT GTT GGG TGT TGT GT-RNH2 is dose-dependent, with an EC50 24 hr after dosing of approximately 4 uM for 800 U/ml interferon-γ. The reverse complement II 5' AC ACA ACA CCC AAC ACA ACC AAC CCC-RNH? did not show activity. Oligodeoxynucleotide I inhibits induction of MHC-I by interferon-γ, but does not inhibit induction by either interferon-α or interferon-β. Four other oli-godeoxynucleotides were also evaluated, and three showed activity against interferon-γ at 25 μM.