Fluoxetine (Prozac) is a new antidepressant, first marketed in the United States in January 1988. Only limited toxicologic information during a fluoxetine overdose is available. The goal of this prospective multi-center study was to develop a toxicity profile of initial signs and symptoms observed in fluoxetine overdose. A standardized data collection form was used on all patients ingesting fluoxetine as reported to four poison centers. Information obtained included age, dose, co-ingested drugs, presenting symptoms, vital signs, EKG abnormalities and lab values. Of the 127 cases of acute fluoxetine overdose collected, 106 cases met the criteria of the study. Of these, 69/106 ingested other drugs, including ethanol and 37/106 ingested fluoxetine alone. Of the latter group, the amounts ingested ranged from 20 to 1500 mg. It was observed that 48.6% (18/37) remained asymptomatic, 16.2% (7/37) were sleepy, 24.3% (9/37) had a sinus tachycardia (of 100 beats per minute or greater), and 8.1% (3/37) had a diastolic pressure over 100 mm Hg. Data collection is ongoing. Based upon our initial experience, fluoxetine in overdose appears to be relatively benign.