High concentrations of homocysteine damage endothelial cells and lower concentrations increase vascular smooth muscle cell (VSMC) growth. This study investigated the effects of various concentrations of homocysteine on endothelial cells (VECs) and VSMCs in terms of cell survival, proliferation, and function. VECs and VSMCs from porcine thoracic aorta were studied. These cells were exposed to homocysteine in concentrations of 20 microM, 400 microM, and 1 mM every 8 h for 24 h, and its effect on cell survival, proliferation, and function were studied using methylthiazoletetrazolium assay, [3H]-thymidine incorporation test, and 6-keto-prostaglandin F1alpha enzyme-linked immunosorbent assay for VECs, and platelet-derived growth factor (PDGF) enzyme-linked immunosorbent assay for VSMCs, respectively. In VECs, 20 microM of homocysteine reduced the viable cell count to 95 +/- 31%, 400 microM reduced it to 89 +/- 35%, 1,000 microM reduced it to *58 +/- 29% (control = 100 +/- 30%, n = 18, *p < 0.05). In VSMCs, 20 microM of homocysteine slightly increased the viable cell count to 106 +/- 30%, but there was no statistical significance; 400 microM of homocysteine reduced the viable cell count to *74 +/- 29%, 1,000 microM to *50 +/- 24% (control = 100 +/- 28%, n = 18, *p < 0.05). In VECs, 20 microM of homocysteine reduced [3H]-thymidine uptake by 98 +/- 14%, 400 microM reduced it by *82 +/- 17%, 1,000 microM reduced it by *66 +/- 17% (control = 100 +/- 12, n = 6, *p < 0.05), respectively. But in VSMCs, 20 microM of homocysteine significantly increased [3H]-thymidine uptake (*131 +/- 16%), and thereafter, homocysteine decreased VSMCs [3H]-thymidine uptake, 400 microM by *24 +/- 7%, 1,000 microM by *29 +/- 10% (control = 100 +/- 16, n = 6, *p < 0.05), respectively. Homocysteine decreased VEC prostacyclin secretion in a dose-dependent manner, 20 microM by 105 +/- 0.65 pg/100 microl, 400 microM by *100 +/- 2.37 pg/100 microl, 1,000 microM by *93 +/- 2.54 pg/100 microl (control = 107 +/- 1.26 pg/100 microl, n = 6, *p = 0.007). In VSMCs, 20 microM of homocysteine slightly increased PDGF secretion by 62.2 +/- 20.7 pg/100 microl, but there was little statistical significance (p = 0.13); 400 microM of homocysteine reduced PDGF secretion by *28.9 +/- 10.7 pg/100 microl, and 1,000 microM reduced it by *21.3 +/- 4.7 pg/100 microl (control = 54.5 +/- 9.3 pg/100 microl, n = 6, *p < 0.05). High concentrations of homocysteine damaged both VECs and VSMCs with respect to cell survival, proliferation, and function. By increasing exposure to homocysteine, it was shown that physiologic high concentrations of homocysteine enhanced VSMC proliferation.