Twenty-one patients fulfilling the Center for Disease Control criteria for chronic fatigue syndrome (CFS) were examined in a controlled study. Viral antibodies and tests evaluating the immune system were investigated in the patients and in a control group of 21 sex- and age-matched individuals. Production in vitro of the predominantly T-cell-derived cytokines interleukin-2 and interferon-gamma was significantly higher in patients with CFS compared the control group. Furthermore, the serum concentrations of IgA and IgE were significantly lower in patients with CFS; however, the values were within the normal reference range. All other variables were similar in the two groups. This study does not suggest a clearly disordered immune system or a chronic viral infection as a major pathogenetic factor in CFS. Longitudinal studies of immunological and virological parameters in CFS are warranted as are studies on patients that are severely handicapped.