Family history data were collected on first-degree relatives of 78 patients with bipolar I disorder (BD) and substance use disorder (SUD), 47 with BD only, and 35 with SUD only. The prevalence of psychiatric disorders was significantly higher in first-degree relatives of patients with BD + SUD (64%) and BD (61%) compared with first-degree relatives of SUD patients (20%). The prevalence of alcohol misuse was significantly higher in first-degree relatives of patients with BD + SUD (23.1%) and SUD alone (28.6%) compared to first-degree relatives of patients with BD (4.3%). Our findings suggest that BD and SUD do not share familial risk factors.