Pulmonary endothelial cell function (ECF) studies have been shown to be a sensitive indicator of chronic lung injury. We attempted to correlate changes in 5-hydroxytryptamine (5HT) uptake with an acute oxygen radical-mediated lung injury in dogs. Beta-d glucose/glucose oxidase was injected intravenously in an experimental group (n = 10), while the control group (n = 5) received saline. 5HT uptake, measured using a multiple indicator dilution technique before and 20 min after injection, was calculated for both the percent total uptake and the peak extraction ratio of 5HT during a single passage through the lung. The mean pulmonary and systemic arterial pressures (PAP, SAP), total pulmonary resistance (TPR), extravascular lung water (EVLW), and wet-to-dry weight ratios were also determined. The experimental group showed an acute rise in PAP and TPR and a fall in SAP after the injection, all returning to normal by 20 min; total 5HT uptake fell from 81 +/- 2.3% to 47 +/- 6.5% (p = 0.0002) as did the peak extraction ratio from 0.87 +/- 0.013 to 0.44 +/- 0.066 (p = 0.0001). No change in 5HT uptake was observed in the control group. EVLW did not change in either group, but wet-to-dry weight ratio was elevated in the experimental group (5.21 +/- 0.12 versus 4.73 +/- 0.06, p less than 0.01). ECF studies of 5HT uptake appear to be a sensitive indicator of acute lung injury in this large-animal, oxygen radical-induced injury model.