Low-density lipoprotein has proliferative effects on vascular smooth muscle cells and thus may play a role in the pathogenesis of atherosclerosis and hypertension. In order to investigate the underlying mechanisms, we studied the influence of low-density lipoprotein on intracellular free calcium, intracellular pH and the rate of DNA synthesis in cultured vascular smooth muscle cells of the rat aorta. The low-density lipoprotein (1-30 micrograms/ml) caused a dose-dependent increase in intracellular calcium and affected the intracellular pH accordingly. In addition, a marked low-density lipoprotein-induced increase in 3H-thymidine incorporation into DNA was observed. It is concluded that low-density lipoprotein, apart from its classical role as a cholesterol-transporting vehicle, enhances cellular processes leading to cell proliferation.