The recommended and commonly used methods for the isolation of platelets from whole blood do not harvest a representative platelet population. There is evidence that these methods may result in the loss of a functionally more active platelet subpopulation. We describe a method whereby a completely representative population of platelets was isolated from the whole blood of 28 normal human volunteers by repeated washing of platelets from the red-cell layer. The harvesting efficiency was 98.3% +/- 2.8%. The platelets were labelled with 111In-oxine in a saline milieu with a labelling efficiency of 86.4% +/- 6.8%. The disappearance of reinjected labelled autologous platelets from the circulation was almost linear, and the mean platelet survival was estimated to be 224 +/- 23 h. At equilibrium, 61% +/- 12% of the labelled platelets were recovered from the circulation. The in vivo distribution at equilibrium and the sites of sequestration of the senescent labelled platelets were determined by geometric-mean whole-body quantification in six of the volunteers. This improved method permits accurate quantification of organ 111In radioactivity. Following reinjection, the labelled platelets pooled in the spleen and the accumulated activity can be presented by a single exponential function. At equilibrium, 31.1% +/- 6.1% and 9.6% +/- 1.2% of the platelets were in the spleen and liver, respectively. Splenic and hepatic radioactivity increased significantly with time, and at the end of the platelet life span, 35.6% +/- 9.7% and 28.7% +/- 8.3% of the labelled platelets were sequestrated in these organs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)