Fatigue occurs in many patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases and may be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion. It can be restrictive and severely disabling. We recently found more than 3/4 of systemic lupus erythematosus patients to be significantly affected by this phenomenon. We hypothesized that fatigue in patients with RA might be comparable to sickness behavior in animals possibly caused by disturbances in interleukin-1 beta signaling pathways and thus accessible to blockade by biologic agents. This study compared measures of disease behavior and fatigue symptoms in eight RA patients before and at three time points during treatment with daily administration of anakinra.