Young men dying suddenly and autopsied by the coroner sometimes have coronary thrombosis at a relatively early stage of arteriosclerosis. The plaques under such thrombi often have a complex of features, a) rupture, b) hemorrhage, c) medial destruction, d) nodular collections of foam cells, e) calcification, f) cellular infiltrates of the fibrous cap, fibrous base and adventitia, and g) a newly described kind of phagocytic activity at the boundary between the necrotic core and the fibrous base of the plaque. Commonplace innocuous plaques in most middle and old aged subjects without heart disease also often have some of these features. What structural characteristics might distinguish rare thrombogenic from commonplace innocuous plaques? Twenty-one thrombotic plaques from 18 cases of sudden coronary heart disease (CHD) death were histologically compared with 129 nonthrombotic plaques from these same 18 cases, 85 plaques from 23 cases of CHD death due to arteriosclerotic occlusion, and 94 plaques from 22 cases having no CHD. Plaques with thrombosis all had necrotic cores; plaques for comparison with these were therefore chosen all to have necrotic cores. Rupture and hemorrhage were found in 90% of thrombotic plaques, with mixing of plaque gruel and blood in the thrombus. Medial destruction, foam cells and calcification (features c, d, and e) were commonplace in all types of plaques. Small-cell infiltrates and atherophagocytosis (features f or g) were found in 72-94% of the 21 thrombotic plaques, but only in 18-24% of the 94 not CHD plaques. The necrotic core, characterized by crystalline cholesterol, appears to incite cellular responses in some plaques but not others; those responses distinguish thrombogenesis. The findings imply that thrombogenicity and its accompanying plaque cellularity are incited not by cholesterol, but by some trace or minor component of the plaque gruel of the necrotic core. The possibility of testing these hypotheses by practical methods has been shown to be feasible.