Abnormalities of immune system compartments were determined in 12 patients with Huntington's disease (eight males, four females; age 42.4 ± 11.7 years) and 11 controls (7 males, 4 females; age 47.0 ± 12.0). All patients were free from infectious diseases. Serum concentrations of a panel of serum soluble markers of immune activation were investigated, namely neopterin, 55-kDa-type soluble tumor necrosis factor receptor (sTNF-R), interleukin-2-receptor (sIL-2R), kynurenine, tryptophan, immunoglobulins (Ig) A, M and G as well as routine laboratory tests. Compared to controls, we found significantly higher serum levels of IgA (p < 0.01), sTNF-R, sIL-2R, neopterin, and complement component C3 (all p < 0.05), and serum tryptophan was decreased (p < 0.001). Higher concentrations of circulating immune complexes, cardiolipin antibodies, IgM, neopterin and lower tryptophan were associated with loss of cognitive function as assessed by the minimental-test. Five patients died within 1 year after measurements were performed. In these patients IgM, circulating immune complexes and neopterin concentrations were higher compared to survivors and serum tryptophan was lower. The data indicate an activation of various immune system compartments in Huntington's disease and that systemic immunological alterations might be important in the course of the disease.