Previous studies have yielded mixed evidence as to whether rapid-cycling bipolar disorder (four or more episodes per year) is associated with a distinctive pattern of patient characteristics and familial aggregation of affective disorder. In this study, Family History Research Diagnostic Criteria (FH-RDC) were used to interview 165 patients with rapid-cycling bipolar disorder, non-rapid-cycling bipolar disorder, or recurrent unipolar depressive disorder about the psychiatric history of 812 adult first-degree relatives. In a validity study, FH-RDC diagnoses were demonstrated to agree reasonably well with best-estimate diagnoses by two psychiatrists/psychologists, based on direct interviews with the Structured Clinical Interview for DSM-III-R. Relatives of patients with recurrent unipolar depression were less likely to have bipolar disorder and more likely to have unipolar depression than were relatives of rapid-cycling or non-rapid-cycling bipolar patients. Rapid-cycling patients were younger and more likely to be female than non-rapid-cycling patients. The relatives of rapid cyclers did not differ significantly from those of non-rapid cyclers in the prevalence of bipolar disorder, unipolar disorder, rapid-cycling bipolar disorder, or substance abuse. However, there were nonsignificant trends for the relatives of rapid-cycling bipolar patients, compared with those of non-rapid-cycling bipolar patients, to have more substance abuse and less bipolar disorder given the presence of affective disorder.