The familial form of hemophagocytic lymphohistiocytosis (HLH) is an inherited disease with disturbed immunomodulation and characterized by fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and coagulopathy, i.e., findings which are similar to many of the reported biological effects of the inflammatory cytokines. Due to the previously shown hypercytokinemia in active H L H with elevated levels of interleukin (IL)-6, tumor necrosis factor-a, and interferon-gamma, it has been suggested that cytokine dysregulation may be of pathophysiological importance. Here we have assayed the serum levels of the members of the IL-l ligand family, the two agonists I L -l a and IL-l p and the antagonist IL-1 receptor antagonist (IL-1 ra), in nine children with HFH and cerebrospinal fiuid (CSF) specimens from four children. Serum IL-1 ra was elevated in all patients with active disease to a degree which correlated well with disease activity. Furthermore, the levels decreased day by day during treatment of a patient who suffered a relapse. Moreover, high levels of IL-l ra were also detected in CSF during active disease. However, IL-l p levels were all within normal limits and circulating I L -l a levels were normal in all but two patients. o