Background: The duration of untreated psychosis (DUP) - the time from onset of psychotic symptoms to the start of adequate treatment - is consistently correlated with better course and outcome, but the mechanisms are poorly understood. Objective: To report the effects of reducing DUP on 2-year course and outcome. Design: A total of 281 patients with a DSM-IV diagnosis of nonorganic, nonaffective psychosis coming to their first treatment during 4 consecutive years were recruited, of which 231 participated in the 2-year follow-up. A comprehensive early detection (ED) system, based on public information campaigns and low-threshold-psychosis-detecting teams, was introduced in 1 health care area (ED area), but not in a comparable area (no-ED area). Both areas ran equivalent 2-year treatment programs. Results: First-episode patients from the ED area had a significantly lower DUP, better clinical status, and milder negative symptoms at the start of treatment. There were no differences in treatment received for the first 2 years between the groups. The difference in negative symptoms was maintained at the 1-year follow-up. There was a statistically significant difference in the Positive and Negative Syndrome Scale negative component, cognitive component, and depressive component in favor of the ED group at the 2-year follow-up. Multiple linear regression analyses gave no indication that these differences were due to confounders. Conclusion: Reducing the DUP has effects on the course of symptoms and functioning, including negative symptoms, suggesting secondary prevention of the negative psychopathologies in first-episode schizophrenia.