Abstract: Human ω-interferon (IFN-ω) has been shown to be well-tolerated in man and to induce reductions of hepatitis C virus RNA levels in a series of human clinical trials. Here we provide an overview of our preclinical safety evaluation of the fully-glycosylated human IFN-ω produced from CHO-SS cells that is currently being evaluated clinically. IFN-ω was not associated with any biologically-relevant adverse effects in a series of 10 safety pharmacology experiments, in the Ames mutagenicity test, in the micronucleus test, or in intraarterial, intravenous, paravenous or subcutaneous local tolerance studies. Acute, subacute, subchronic and reproductive toxicity studies performed in cynomolgus monkeys and rats showed a toxicity profile similar to that of human α interferon (IFN-α). Except for the acute (single-dose) toxicology study, all of the other toxicity studies showed evidence for the formation of anti-IFN-ω antibodies over time in the animals. These antibodies were found to neutralize IFN-ω antiviral activity in vitro in a dose-dependent manner. The average pharmacokinetic parameters following a single subcutaneous dose of IFN-ω in rabbits, rats and monkeys were determined and found to be similar to that of human IFN-α. These findings demonstrate that IFN-ω has a safety profile consistent with that required for its use in man. IFN-ω might be beneficial for the treatment of patients infected with hepatitis C virus who fail to respond to IFN-α or as a first-line treatment option.