Cadmium has a singular ability to promote the functional reconstitution of tissue factor (coagulation factor III) apoprotein with vesicles formed from mixed bovine brain lipids. Cadmium causes rapid release of carboxyfluorescein from lipid vesicles which chromatograph in the included volume of Bio Gel A5m, and also promotes reconstitution of tissue factor with these vesicles. With larger vesicles, which are excluded on Bio Gel A5m, cadmium produces only low levels of reconstitution and leakage. Calcium has been shown to promote only low levels of tissue factor-vesicle reconstitution, and produces only low levels of carboxyfluorescein leakage when compared to cadmium. These results demonstrate that cadmium and calcium interact differently with the small mixed lipid vesicles, and suggest that the cadmium-promoted reconstitution of tissue factor vesicle-complexes accompanies cadmium-induced alterations in vesicle structure. The results also show that cadmium affects large and small vesicles differently.