The platelet dense granule release reaction was monitored by measuring the serotonin content of platelets collected by filtration following release. Sensitive HPLC-fluorometric analysis permitted release to be assessed using small (25-50 microliters) volumes of plasma and whole blood. Release could be examined for periods as short as 1 s due to the rapid stoppage effected by filtration. The half-life of thrombin-stimulated (1 U/ml) release was 2-3 s, the EC50 values observed for thrombin-stimulated release over a 60-s release period were 0.01-0.03 U/ml for diluted whole blood and plasma samples.