Objective: To examine the effects of heparin on smooth muscle cells (SMCs) in explants of varicose, long saphenous vein (LSV). Procedures: Explants of varicose LSV were cultured for 7 days either alone, or with heparin at 10, 100 or 1000 IU/ml (Monoparin). At 7 days, cultured explants were analysed for changes in intimal and medial thickness and by immuno-histochemistry. Comparisons were made with explants at initial isolation and with similar, cultured explants of normal LSV. Results: In normal LSV, by day 7, SMC-derived neo-intimal hyperplasia developed ( p<0.01) with an increase in intimal thickness ( p<0.02) and a decrease in medial thickness ( p<0.001). Heparin at 10 and 100 IU/ml further enhanced this neo-intima formation ( p<0.001). In contrast, at 1000 IU/ml, heparin inhibited neo-intima formation. In varicose explants, the pattern of intimal and medial changes was different. At isolation, varicose LSVs had substantially thicker intimal layers ( p<0.001). When cultured alone, a thicker media developed ( p<0.001) but there was little change in intimal thickness. Heparin at all concentrations had no effect on the thicker medial development seen in controls but did, however, reduce intimal thickness ( p<0.005). Conclusions: The response to heparin in explants of varicose LSV is different from that of normal LSV, which is biphasic and complex.