The preventative effects of bifemelane (4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride) on atherosclerosis in aged rats fed low-calcium diets were investigated. Male 18-month-old Wistar rats were maintained for 90 days on the following: (A) standard diet (n = 7), (B) low calcium, low magnesium, high aluminium diet (n = 8), (C) standard diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6), (D) low calcium and magnesium, high aluminium diet plus oral intubation with 10 mg bifemelane/kg daily (n = 6). All groups were give these diets and water ad lib for 90 days, after which blood samples were taken from the abdominal aorta and samples of aorta were examined for atherosclerotic changes. The serum concentrations of the following were determined: calcium, magnesium, zinc, aluminium, inorganic phosphorus, cholesterol, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, cholinesterase, creatine phosphokinase, blood urea nitrogen and N-terminal parathyroid hormone. The only significant differences between the groups in serum chemistry were reduced concentrations of cholinesterase and magnesium in groups B and D, increased aluminium in group B, and increased N-terminal parathyroid hormone in groups B and D. In groups C and D the atherosclerosis was much improved compared with that in groups A and B. It appears that bifemelane largely prevents atherosclerosis caused by calcium deposition in the arteries of rats fed low-calcium diets, due to its effect in maintaining magnesium and calcium in bones.