Interferon (IFN)-λ1 is a newly described cytokine that is known for its proinflammatory activity in viral infection and in cancer. Because recent studies indicated that IFN-λ can influence significantly the innate and adaptive immune response, we studied IFN-λ in a prototypic systemic autoimmune disease, rheumatoid arthritis (RA). It was found that RA patients had higher mRNA levels in PBMC and higher serum levels of IFN-λ1 in comparison with healthy matched controls and ankylosing spondylitis (AS) patients. Although there was no correlation between serum IFN-λ1 and RA autoantibodies, RA patients that presented knee joint involvement displayed higher serum IFN-λ1 than patients without knee joint involvement, suggesting that abnormally elevated IFN-λ1 levels in RA can associate with knee joint disease.