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Objective. Rapid dose escalation of quetiapine could offer prompt and effective therapy to patients requiring hospitalization for schizophrenia or schizoaffective disorder. This study evaluated the safety, tolerability, and efficacy of a rapid dose escalation of quetiapine to 800 mg/day over 4 days in patients with severe psychotic symptoms diagnosed as schizophrenia or schizoaffective disorder. Methods. In this open-label, multicenter, pilot study, 14 patients aged 18 years or older, requiring hospitalization for schizophrenia or schizoaffective disorder, received quetiapine orally twice daily for 14 days. Quetiapine was administered according to the schedule: 200, 400, 600, and 800 mg/day on the first four treatment days, followed by flexible dosing within the range 400-800 mg/day during the next 10 days. The primary endpoint was to evaluate the safety and tolerability of a fast titration of quetiapine (200, 400, 600, 800 mg/day on the first four treatment days). Effectiveness of a fast titration of quetiapine was the secondary objective of this investigation. Efficacy assessments in the intent-to-treat (ITT) population included changes in the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity of Illness (CGI-S) scores from Day 1 (baseline) to Day 14. Results. In 4 days 14 patients were titrated up to a dose of 800 mg/day. Ten patients were diagnosed with schizophrenia, one subject was suffering from schizoaffective disorder of the depressive type and three patients were diagnosed with schizoaffective disorder of the bipolar type. Eleven patients (79%) completed the study. Two patients discontinued the trial because of non-compliance and one patient because of a prolonged QTcB interval. Overall, 29 AEs were reported during this trial, all were considered mild or moderate in severity. During the first 7 days of the trial, 25 AEs were reported in 11 patients. The majority of AEs were considered as possibly related to the study medication. No deaths or serious adverse events were reported. Physical examination at the last trial visit revealed no clinically relevant changes versus baseline and there were no consistent changes over time in vital signs. The BARS and SAS scores indicated an improvement of EPS during the study. After 4 days of fast titration, the mean total PANSS score decreased from 92.8 at baseline to a value of 87.4, there was a further decrease to 78.2 at endpoint. This corresponds to a statistically significant decrease by 14.6 versus baseline (P<0.01). After 4 days of fast titration, the mean CGI-S score was improved from 4.7 at baseline to a value of 4.3 and improved further to 3.8 at endpoint, corresponding to a statistically significant decrease of 0.9 points versus baseline (P<0.01). Conclusion. In this study, fast titration of quetiapine to 800 mg/day over 4 days was generally well tolerated and effective in reducing psychotic symptoms in patients requiring hospitalization for schizophrenia/schizoaffective disorder.