Various pharmacologic agents have been tried to control proliferative vitreoretinopathy (PVR). However, most are water soluble and cannot be used with silicone oil (SO), a tamponade agent also used in PVR management. We evaluated a lipophilic, antiproliferative drug, BCNU, in regard to its solubility and stability in SO, its release from SO into an aqueous solution, and its effect on cell cultures. BCNU is soluble in SO (peak concentration inμg/ml 1020, 750, and 294 at 37°C, 21°C, and 4°C, respectively), and stable (half-life = 6.7 weeks at 37°C, 17.9 weeks at 21°C). At 4°C, no significant decrease in concentration up to eight weeks was noted. BCNU is released from SO to water (partition coefficient = 10.28±2.16). Its median inhibitory doses (ID50) on bovine retinal pigment epithelial (RPE), rabbit RPE, and subconjunctival fibroblast cells are 13, 1.9, and 15.6μg/ml, respectively. BCNU may be a useful pharmacologic tool to control PVR.