An improved method for labeling human platelets with In-111 oxine is described. The method used modified Tyrode's solution (MTS) as a labeling medium and allowed 86 +/- 7% incorporation of In-111 into platelets, which upon stimulation with ADP aggregated 66 +/- 15% of control platelets. This compared favorably with the 5% radioactivity uptake in plasma and the 36 and 55% aggregability of platelets labeled in saline and citrated saline, respectively. The influence of parameters affecting the platelet aggregability were examined. The studies revealed that excess of oxine (50 microgram oxine/1.6 x 10(9) platelets in 1 ml MTS), and centrifugation at greater than 1000 g, reduced platelet aggregability. Excess of oxine also caused a dose-dependent release of In-111 from platelets labeled either in MTS or in plasma, but 4 millimol EDTA did not. Release of In-111 upon aggregation of platelets labeled in either medium was negligible.