Our objective was to begin to elucidate the interrelationship between psychoactive substance use disorders (PSUD) and schizophrenia in patients who concurrently have both disorders. A series of 29 psychiatric inpatients with concurrent Research Diagnostic Criteria (RDC)-diagnosed schizophrenia and PSUD (PSUD/S patients) were evaluated with rating inventories including the Schedule for Assessment of Negative Symptoms (SANS) and the Schedule for Assessment of Positive Symptoms (SAPS). Subjects had chronic schizophrenia with a mean duration of 9.9 years, and virtually all (93.1%) regularly abused cocaine and alcohol, as well as marijuana. The majority of subjects (58.6%) had mixed-syndrome typology, as defined by Andreasen; 24.1% had negative syndrome; and 16.7% had positive syndrome. Contrary to predictions, negative-syndrome PSUD/S patients had fewer years post-onset of schizophrenia than those patients with positive syndrome. In contrast to other schizophrenic patients, in whom the trajectory of symptoms is believed to change from a predominance of positive symptoms to a predominance of negative symptoms over the course of illness, in a sample of patients with comorbid PSUD/S we found the opposite pattern. This may have implications in the development of PSUD among certain schizophrenics, and may help to guide both psychiatric and substance abuse treatment of such patients.