We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [LDLR^−/−] and express a human apolipoprotein B-100 (apoB) transgene [Tg(apoB^+/+)] with or without an apo(a) transgene [Tg(apoa^+/−)]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (i) LDLR^−/−, (ii) LDLR^−/−;Tg(apoa^+/−), (iii) LDLR^−/−;Tg(apoB^+/+), and (iv)LDLR^−/−;Tg(apoB^+/+);Tg(apo^+/−). The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the LDLR^−/− and LDLR^−/−;Tg(apoa^+/−) mice (1.0 ± 0.2% vs. 1.4 ± 0.3%). However, the LDLR^−/−;Tg(apoB^+/+) mice had ≈15-fold greater mean lesion area than the LDLR^−/− mice. No significant difference was found in percent lesion area in the LDLR^−/−;Tg(apoB^+/+) mice whether or not they expressed apo(a) [18.5 ± 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 ± 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of LDLR^−/−;Tg(apoB^+/+) mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that LDLR^−/−; Tg(apoB^+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.