Serotonin is released by activated platelets and may promote platelet aggregation and epicardial coronary artery constriction in animal models. Serotonin may have similar effects in humans and, thus may be a mediator of certain ischemic syndromes. However, the role of serotonin in human ischemic heart disease has not been studied. Since evaluation of transcardiac serotonin metabolism requires that blood samples be obtained through long catheters, it is possible that artifactual changes in serotonin concentration could occur because of platelet activation in the catheters themselves. Accordingly, to determine if serotonin could be measured through long catheters without artifactual changes, the authors obtained paired blood samples by gentle aspiration through a large bore steel needle and a 100-cm polyurethane catheter placed in the femoral vein of 13 patients. All samples were processed to obtain platelet-poor plasma and then analyzed by a sensitive radioenzymatic assay. Blood sampling through long catheters did not cause a systematic alteration in plasma serotonin concentration. Mean serotonin concentration from the femoral vein through a needle was 22.3 +/- 26.55 ng/ml (mean +/- standard deviation), and that obtained through a long catheter was 20.0 +/- 26.29 ng/ml (p = 0.34). The authors conclude that carefully obtaining blood samples through long catheters does not significantly alter the plasma serotonin concentration and thus the accurate measurement of transcardiac serotonin concentrations is possible using these methods.