Study subjects were recruited at four recruitment sites including University of Connecticut Health Center (UConn, Farmington, CT), Yale University School of Medicine (APT Foundation, New Haven, CT), Medical University of South Carolina (MUSC, Charleston, SC), and McLean Hospital (Harvard Medical School; Belmont, MA). The number of families recruited at each site is: for AA, Yale 153, UConn 140, McLean 43, MUSC 48, and for EA, Yale 101, UConn 152, McLean 45, and MUSC 52. We screened the families based on the belief that at least two siblings in each family would meet diagnostic criteria for cocaine dependence (CD) or opioid dependence(OD) or alcohol dependence (AD) for inclusion in small nuclear family linkage studies. OD families were recruited primarily at the UConn and Yale sites, while CD families were recruited at all sites. Probands with an axis I clinical diagnosis of a major psychotic disorder (e.g., schizophrenia or schizoaffective disorder) were excluded from the study. We also recruited other siblings and parents whenever available regardless of their affection status to increase the power to detect linkage. Each subject provided written informed