The effect of several antineoplastic agents on vascular smooth muscle cell proliferation was studied in vitro. Both fluorouracil and cytarabine produced significant concentration-dependent inhibition of smooth muscle cell proliferation in cultured porcine pulmonary artery in vitro, while cyclophosphamide stimulated growth. For fluorouracil, inhibition was near maximal at a concentration of 13.0 microgram/mL and was seen with both coincubation and 2-hour preincubation of fluorouracil with quiescent cells. Fluorouracil is a promising agent for inhibition of intimal proliferation. Further work is warranted to determine its effect in vivo.