DSM-III-R and proposed DSM-IV schemes for the diagnosis of psychoactive substance use disorders are based largely on the dependence syndrome concept. However, there is an absence of empirical support for the generalizability of the dependence syndrome across substances. This study examines how consistently proposed DSM-IV dependence criteria function to measure dependence across seven substances: alcohol, cannabis, cocaine, stimulants, hallucinogens, sedatives and opiates. Using structured research diagnostic interviews, dependence diagnoses were determined for 295 American subjects in treatment for alcohol/drug problems. Several factor analytic techniques were used to assess whether criteria formed single dimensions and how consistently individual criteria measured dependence across substances. The ability and consistency of criteria to measure a continuum of severity across substances were also assessed. Only subjects who used the substance at least six times were entered in the analyses. Overall, results provide strong support for the DSM approach for alcohol, cannabis, cocaine, stimulants, sedatives and opiates, but not for hallucinogens. Results indicate that a single strong factor adequately described the criteria for these six substances. All criteria loaded strongly and uniformly on single factors indicating that all were good measures of dependence. Criteria provided a dimensional measure of severity based on several indices for these substances. In addition, four criteria provided relatively stable indicators of high or low severity across these substances. Results did not support the use of dependence criteria for hallucinogens as these criteria did not form a single factor. Results suggest that very few hallucinogen users experience an inability to cut down or control use, a key indicator of loss of control.