Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that was introduced in 1986. Certain side effects of this medication-drowsiness, dizziness, abnormal vision, diarrhea, and headache-could affect pilot performance and become a factor in an aviation accident. Our laboratory has determined the distribution of fluoxetine and its desmethyl metabolite, norfluoxetine, in various postmortem tissues and fluids from 10 fatal aviation accident cases. When available, 11 specimen types were analyzed for each case, including blood, urine, vitreous humor, bile, liver, kidney, skeletal muscle, lung, spleen, heart muscle, and brain. Blood fluoxetine concentrations in these 10 cases ranged from 21 to 1480 ng/mL. The distribution coefficients for both fluoxetine and norfluoxetine, expressed as specimen/blood ratios, were determined. The distribution coefficients for fluoxetine were determined to be 0.9 +/- 0.4 for urine, 0.10 +/- 0.03 for vitreous humor, 9 +/- 1 for bile, 38 +/- 10 for liver, 60 +/- 17 for lung, 9 +/- 3 for kidney, 20 +/- 5 for spleen, 2.2 +/- 0.3 for muscle, 15 +/- 3 for brain, and 10 +/- 2 for heart. To our knowledge, this is the first report presenting the distribution of fluoxetine in humans at therapeutic concentrations.