Depression has been associated with increases in circulating cytokines in younger adults, and there is evidence for prefrontal inflammation in late-life depression. The authors tested the hypothesis that levels of cytokine interleukin-1β (IL-1β) would be higher in subjects with late-life major depression. Serum levels of IL-1β were measured in three groups of subjects who were older than 60: 19 subjects with major depression, 20 subjects with subsyndromal depression, and 21 healthy comparison subjects. The Montgomery-Åsberg Depression Rating Scale and the Geriatric Depression Scale were used to assess severity of depression. Compared with healthy subjects, those with major depression had significantly higher levels of IL-1β (170%); the higher levels of IL-1β strongly correlated with current depression severity. There were no significant differences between subjects with subsyndromal depression and the other two groups. These findings support the existence of an inflammatory response, which may be state dependent, in late-life depression.