Aims To test in vitro, the constrictor and relaxation responsiveness of variously diseased segments of human saphenous vein from patients with varicose vein disease. Methods The vein segments were derived (i) from the inguinal saphenous vein (valvularly incompetent and slightly dilated; tissue A); (ii) from the distal end of the lower leg just above the medial ankle (competent; tissue B) (iii) from a tributary to the long saphenous vein just below the knee (dilated, incompetent and overtly varicose; tissue C). The contractile responses were tested with phenylephrine (an alpha -adrenergic receptor agonist) and aescin. a clinically used phlebotonic drug derived from horst chestnut extract. Relaxant responses were tested with acetylcholine and sodium nitroprusside. Results Both contractile agents contracted vein segments from the inguinal and ankle area with similar potency and efficacy, but were virtually without effect in the overtly varicose segments from the calf. EC50, values (molar concentration of the agonist that produces 50% of the maximum effect) in tissues A and B were 2.9+/-0.3 and 2.5 +/- 0.5 mu mol l(-1) (phenylephrine) and 9.4 +/- 1.0 and 15.9 +/- 2.5 mu mol l(-1) (aescin); the corresponding maximum effects (maximum effect, percent of KCl-induced contraction) were 76 +/- 3 and 70 +/- 4% (phenylephrine) and 70 +/- 2 and 71 +/- 3% (aescin) (P = NS in both cases for A vs B). In tissue C, the maximum effects were 5+/-5% (phenylephrine) and 10 +/- 7% (aescin) of KCl-induced contraction (not significantly different from zero). Acetylcholine-induced relaxation was similar for vein segments ti-om locations A and B. whereas sodium nitroprusside was more effective ill tissue B than A. Conclusions These findings support the notion that abnormalities within the venous wall affect venous smooth muscle contractility. Since competent and incompetent clinically normal vessels show normal contractile responses. whereas varicose vessels are not responsive to vasoactive drugs, it is likely that pharmacological treatment regimens are effective in early, but not in late stages of the disease.