OBJECTIVE: Familial risks of depression have been assessed in small case-control studies, usually based on reported, but not medically verified depressions in family members; thus the degree of familial clustering for these diseases remains to be established. METHODS: We conducted a nationwide study on familial risks of depression linking the Multigeneration Register of 0-72-year-old individuals to the Hospital Discharge Register for diagnosed depression patients in Sweden from 1987 to 2004. Standardized incidence ratios (SIRs) were calculated for affected singleton siblings, twins, and spouses by comparing those whose siblings or spouses had no recorded hospitalization for depression. RESULTS: A total of 60 477 hospitalized cases and 3849 affected siblings were identified with a familial SIR of 2.95, which was independent of sex, age at diagnosis, and age differences between siblings. When both siblings were diagnosed with manic, bipolar, or major depression, the SIRs were 5.87, 10.23, and 2.79, respectively. The SIR for twin pairs was 4.57. The SIR for spouses was 1.76. CONCLUSION: The significantly higher risk for siblings of depression patients than that for spouses suggests that heritable effects highlight familial susceptibility to this disease. To what extent it also contributes to familial depression remains to be established. The anticipated gene-environment interactions with sufficient sample sizes needs to be accommodated in future etiological studies on depression.