Stimulant abuse among chronic schizophrenics presents special problems for both clinicians and health care systems, but there is little systematic treatment of cocaine dependence among chronic schizophrenics, determine if any beneficial effects persist after medication is stopped, and what baseline subject characteristics might predict outcome. 80 male schizophrenic outpatients currently dependent on cocaine and on stable doses of depot neuroleptic will be randomly assigned to receive either desipramine or placebo double-blind for three months, with weekly group therapy for all subjects. Desipramine dose will be titrated upwards to achieve a target plasma level of 140-220 ng/ml, with desipramine levels assayed every 1-2 weeks. After baseline assessments to confirm schizophrenia and cocaine dependence by Structured Clinical Interview for DSM IIIR, assess current psychopathology (BPRS, Hamilton Depression and Anxiety Scales, Scales for Assessment of Negative and Positive Symptoms) and medical condition (history and physical exam, blood and urine tests, EKG), and characterize recent drug use and psychosocial functioning (Addiction Severity Index), subjects will return weekly to assess cocaine craving and use (self-report, urine toxicology) and physical and psychological symptoms (SCL-90). After the 3-month treatment period, subjects will return quarterly for 1 year follow-up with repeat of baseline assessments. Major outcome variables will include time abstinent from cocaine, level of psychopathology, overall psychosocial functioning (ASI score), and treatment compliance. Data comparing desipramine and placebo groups will be analyzed.\ by ANCOVA, with baseline values of major prognostic variables used as covariates. Multivariate analysis will be used to determine which baseline variables might help predict treatment response and outcome. Should desipramine prove effective, it would significantly improve the treatment of this group of dual diagnosis schizophrenic patients, and help determine whether cocaine use exacerbates schizophrenia or is an attempt at self-medication for depression or negative symptoms.