The anti-atherogenic effect of NIP-200 3,5-dimethyl-4,6-diphenyl-tetrahydro-2H-1,3,5-thiadiazine-2-thione ) was studied in experimental models of 1% cholesterol diet (HCD)-fed rabbits. Interference with growth of the animals did not occur in NIP-200-treated rabbits. NIP-200 had no effect on plasma total cholesterol (TC), triglyceride, free cholesterol and phospholipid during the entire experimental period. However, NIP-200 increased high density lipoprotein-cholesterol (HDL-C) at 1, 2, 4 and 6 weeks, although the average rate of increase was not statistically significant. Percentage surface areas of atherosclerotic lesions on the aorta in NIP-200-treated rabbits (26 +/- 6%) was significantly lower than those in HCD-fed rabbits (48 +/- 8%) (P less than 0.05). Histological studies indicated that NIP-200 prevented intimal thickening, proliferation of elastic fibers and fatty necrosis. Thus, NIP-200 prevented the progression of atherosclerosis without affecting the serum TC. The above results suggest that the improvement of lipoprotein metabolism on the arterial wall and the prevention of migration and proliferation of arterial smooth muscle cells may also be important factors in the progression of atherosclerosis.