There are an increasing number of reports on an association between the alteration of circulating cytokine levels and pathophysiology of psychiatric disorders. Plasma concentrations of interleukin (IL)-18 were measured in 13 nonmedicated patients with psychiatric disorders. There was a significant elevation of IL-18 levels in patients with major depression (n = 8) and panic disorder (n = 5), compared with normal controls. The mean IL-18 value of our psychiatric patients was comparable with that of various somatic disorders reported. We suggest that the elevation of plasma IL-18 levels reflects the increased production and release of IL-18 in the central nervous system under stressful settings. We propose that the measurement of IL-18 plasma levels may provide a useful index for the involvement of immune system in psychiatric disorders.