Psychiatric comorbidity with drug dependence has been widely documented. In the present study, we reanalyze DSM-III-R diagnostic data on middle-aged male twin pairs from the VETR study using latent class methods. We identify four subtypes based on 15 diagnostic categories. We then show that these subtypes are strongly associated with differential rates of transitions in drug use histories, with increased risks in relatives for depression, alcohol, drug and ASPD, as well as with a variety of non-normative and deviant behaviors in youth and in adulthood. We use the result of these analyses to show how the use of a particular drug disorder phenotype for selecting cases could impact final sample composition.