The valid measurement of the concentration of serotonin (5-HT) in blood pla
sma is important when using the platelet as a model for the serotonergic ne
uron. The assay is hampered by the release of 5-HT by (residual) platelets
during the preparation for assay. We developed an isopycnic method that sep
arates cells gently and completely from plasma by centrifuging a diluted Pe
rcoll density-gradient to which whole blood was added. In this study this:
method was compared with the usual differential centrifugation method. The
isopycnic method on average resulted in nine times lon er levels of plasma
5-HT. This difference was linearly related to the number of residual platel
ets in plasma after differential centrifuging. The proportion of intra-indi
vidual variation decreased three-fold. Therefore, the use of a Percoll dens
ity-gradient may lead to a more precise and more accurate estimate of the l
evel of plasma 5-HT. Copyright (C) 2000 John Wiley & Sons, Ltd.