Methods are needed for screening patients at risk for thrombo-embolic diseases. We present an assessment of the relative usefulness of platelet shape distribution and mean volume measurements for probing abnormalities in ischemic heart disease (IHD). Platelet morphology in whole blood (WB) from the antecubital vein and/or abdominal aorta, and citrated platelet-rich plasma (PRP), which have been fixed by 4 volumes 0.8% glutaraldehyde-Tyrodes, pH 7.4, is compared for 17 healthy and 13 IHD donors: (I) 6 post-myocardial infarction (2-16 days), 1 acute coronary insufficiency (7 days) and (II) 6 angiographically characterized coronary artery disease. Platelets were examined under phase contrast microscopy classified as discocytes (D), disco-echi- nocytes (DE) and sphero-echinocytes (SE). WB of IHD donors has fewer D than WB from healthy donors (27(5-57)%* vs 71 (65-80%); *mean (range)) and more SE (24(6-65)% vs 1(0-8)%). Although platelet morphology in PRP from healthy donors Was similar to that of WB, PRP from TED donors contained fewer SE (3(0-11)%) and D (52(20-87)%) than WB. Platelet mean volumes, measured by microscopy, were increased by <7% for IHD donors. Rabbits with induced acute thrombosis (indwelling catheter model) studied at 2 hrs, 24 hrs, 1 day and 5 days showed no alterations in platelet morphology distribution evaluated in fixed whole blood, from either normal (4) or sham-operated (4) rabbits. The distributions in morphologies were essentially identical to those seen for normal human donors. These results indicate that changes in platelet morphology in IHD (i) are best measured in whole blood, (ii) probably do not reflect acute thrombo-embolic events and, (iii) are much larger than the changes in platelet mean volume, suggesting that morphology is the more sensitive probe for abnormalities in IHD.