Coronary heart disease secondary to atherosclerosis is the leading cause of death for men in the United States. Using a new, nontransgenic, non-fat-fed mouse model of hyperlipidemia and atherosclerosis developed in our laboratory, we investigated the effect of sex on lipid profiles and subsequent aortic atherosclerotic lesion formation. Female and male C57BL/6 mice, which consumed a low-fat diet, were treated with either normal saline or poloxamer 407 (P-407), a triblock copolymer comprised of poly(oxyethylene) and poly(oxypropylene) units, for 4 months. Blood samples were obtained at 0, 1, 2, 3, and 4 months, whereas hearts and livers were harvested only at 4 months, because this model requires approximately 4 months for significant atheroma formation. P-407-treated mice of either sex demonstrated a profound increase in plasma cholesterol and triglyceride; at 3 and 4 months the plasma lipids were significantly (p < 0.05) higher for male mice compared with female mice. Aortas retrieved from P-407-treated mice of either sex after 4 months demonstrated a significant (p < 0.001) increase in the mean atherosclerotic lesion size compared with their respective saline-treated controls, but there was no significant (p > 0.05) difference between lesion sizes for P-407-treated male mice (1.02 +/- 0.074 x 10(5) microm(2)) compared with P-407-treated female mice (1.14 +/- 0.28 x 10(5) microm(2)). Livers harvested at 4 months from either sex of P-407-treated mice displayed no damage to hepatocytes but increased proliferation of macrophages (Kupffer cells), which contained sequestered lipids. Thus, male C57BL/6 mice form atherosclerotic lesions as extensive as female mice in the P-407 mouse model of atherosclerosis.