In some patients with thrombocytopenia, it is difficult to determine whether the condition is caused by underproduction of platelets (reduced numbers of megakaryocytes) or an increase in the rate of their destruction (normal or increased numbers of megakaryocytes). A non-invasive test to help distinguish between these two categories of thrombocytopenia would be useful. We related the plasma concentration of glycocalicin, a fragment of the platelet-membrane glycoprotein Ib, to the mechanism of thrombocytopenia by evaluating bone marrow megakaryocyte content and measuring platelet life span. Plasma glycocalicin was measured with a monoclonal antibody to the glycocalicin component of platelet glycoprotein Ib. The mean (+/- SD) plasma concentration of glycocalicin in 34 healthy controls was 87 +/- 20 percent of the level in pooled normal plasma (range, 52 to 127 percent). All of eight patients with aplastic anemia or amegakaryocytic thrombocytopenia confirmed by examining bone marrow (in all patients) and by determining the life span of autologous platelets (in six patients) had glycocalicin levels significantly below the normal range (5 to 27 percent). In contrast, each of 25 patients with thrombocytopenia thought to be caused by a reduction in platelet life span, whose bone marrow contained normal or increased numbers of megakaryocytes, had glycocalicin levels that fell within or above the normal range (48 to 261 percent). There was no overlap of values between the two patient populations. These studies indicate that the measurement of plasma glycocalicin may be a useful adjunct in classifying thrombocytopenic disorders.