This study was designed to develop and validate a new computerized version of the Symptom Driven Diagnostic System for Primary Care (SDDS-PC) and examine its feasibility in primary care practice. One thousand and one patients (ages 18-70) coming for routine care to Kaiser-Permanente were screened on a self-administered symptom scale for major depression, alcohol and drug dependence, generalized anxiety, panic and obsessive compulsive disorders, and suicidal behavior. The screen was followed up by a brief diagnostic interview, administered by a nurse, which yielded a one-page summary of positive symptoms and a provisional computer-generated diagnosis for the physician. The physician reviewed the summary results and made a diagnosis. The nurse and physician were blind to the screen results. Patients were reinterviewed within 96 hours by a mental health professional (MHP) blind to previous results. The nurses’ interviews ranged between 1.5 and 3.5 minutes for a screened positive diagnosis. Agreement between the nurse and physician diagnoses was excellent to moderate. Disagreement was usually in the direction of the physician ruling out major mental disorders in favor of subsyndromal or medical explanations. Only rarely did physicians diagnose disorders not detected by the nurse interview. Agreement between physician and MHP was moderate. Physicians using the SDDS-PC seldom made diagnoses that were not confirmed by the independent assessment of the MHP. The SDDS-PC may facilitate recognition of psychiatric disorders and minimize the physician’s time in information gathering.