OBJECTIVE Fibromyalgia (FM) syndrome may be part of an "affective spectrum disorder." The diseases in this group have in common high rates of major depression in first degree relatives (FDR) and a response to antidepressant treatment. In this familial aggregation study, we tested the hypothesis that depression in patients with FM is related to a family history of depression or alcoholism in their FDR. METHODS To assess the relationship between FM and lifetime histories of depression (DEP) and alcoholism (ALC), personal and family histories of mood and substance use disorders were obtained from 60 probands with FM. DEP and ALC among the probands were diagnosed using the Schedule for Affective Disorders and Schizophrenia, a standardized, structured psychiatric interview, and the Research Diagnostic Criteria (RDC). Family psychopathology in the FDR (parents, full siblings, children) was assessed using the Family History RDC. The odds ratio (OR) for DEP and/or ALC in FDR of probands with a history of DEP versus those without DEP were calculated. Confidence intervals (CI) not including 1 were significant at p < 0.05 (95% CI). RESULTS The odds of identifying FDR with DEP and/or ALC were significantly higher among probands with FM with a lifetime history of DEP than among probands with FM who had no history of DEP (OR = 2.10, 95% CI = 1.23-3.57). This may be accounted for by the significantly higher odds for ALC among the FDR of probands with both FM and DEP compared with the FDR of probands with FM but no history of depression (OR = 2.30, 95% CI = 1.21-4.37). Although alcoholism was increased in the FDR of probands with FM with a history of depression, the odds for DEP were nonsignificantly higher among these FDR (OR = 1.71, 95% CI = 0.87-3.31). OR in the same range of magnitude were obtained when the data were analyzed by family unit, but these results were not statistically significant. CONCLUSIONS Our data suggest that the tendency toward DEP in patients with FM may be a manifestation of a familial depressive spectrum disorder (alcoholism and/or depression in the family members), not simply a "reactive" depression secondary to the pain and other symptoms.