We evaluated an automated method (XE-2100 automated blood cell counter equipped with a laser and upgraded software, Sysmex, Kobe, Japan) to quantify the high fluorescent platelet fraction percentage (HFPF%) as an indicator of platelet production. The mean HFPF% value was 3.1 in 80 healthy subjects (95% confidence interval, 2.8%-3.5%). The coefficient of variation was less than 10% for elevated values and 10% to 20% for normal values. Sample stability was up to 48 hours. We tested the HFPF% in 171 patients with thrombocytopenia. The highest values were found in patients with autoimmune thrombocytopenia and disseminated intravascular coagulation, although HFPF% also was increased in patients with regenerating marrows. In other patient groups with decreased platelet production, the HFPF% was within the normal range. The HFPF% was predictive in the evaluation of thrombocytopenia. We found elevated HFPF% values in disorders associated with increased platelet production, particularly associated with platelet destruction, and normal values in disorders associated with decreased platelet production. The results are precise; testing can be performed as readily as a CBC count using an EDTA-anticoagulated blood sample.