We have observed that NPC-1S669, a leucine derivative with anti-inflammatory activity, reduced the proliferation of human aortic smooth muscle cells (HASMCs) in culture. We used a colorimetric assay and tritiated thymidine to measure the cell density and proliferation of HASMC cultures treated with this agent. We also studied the effect of NPC-15669 on the proliferation and migration of human aortic endothelial cells (HAECs). Subconfluent HASMC cultures were growth arrested for 2 days. On the third day, growth was stimulated with either growth media (medium Ml99 containing 10% fetal bovine serum [FBS]), human platelet-derived growth factor (hPDGF), or fibroblast growth factor (FGF) in the absence or presence of NPC-15669 (0.1-50fiM).Regardless of the stimulating agent for HASMCs (FBS, hPDGF, or FGF), NPC-15669 at concentrations of 10-25/xMcaused a significant reduction in thymidine incorporation (36.7% and 77.2% in 10pMand 25fiM, respectively;p<0.005) and cell density (25–87%,p<0.001) compared with control. NPC-15669 did not, however, have an effect on the rate of proliferation or migration of HAECs, even at concentrations up to 50fiM.Two other anti-inflammatory agents, aspirin and dexamethasone, caused substantially and significantly less inhibition, even at high concentrations (50 and 25/iM, respectively). This study demonstrates that in vitro, NPC-15669 significantly inhibits HASMC proliferation but has no effect on proliferation or migration of HAECs.