OBJECTIVE: The aim of the study was to compare the mechanical and functional properties of isolated small stem villous arteries from the placentas of women who smoked heavily (>/=15 cigarettes/d) during pregnancy with those from the placentas of nonsmokers. STUDY DESIGN: Isolated stem villous arteries were mounted in small-vessel myographs. Circumference-tension relationships were established with 124 mmol/L potassium chloride. Concentration-response curves were obtained for endothelin 1, prostaglandin F2alpha, vasoactive intestinal peptide, corticotropin-releasing hormone, sodium nitroprusside, and cadmium chloride. The effect of nitric oxide was examined with N omega-nitro-l -arginine. RESULTS: Stem villous arteries from the heavy smoking group developed a significantly lower tension than did those from nonsmokers at 6 of 9 steps of the circumference-tension experiment (P <.05). Endothelin 1 evoked a significantly greater maximum vasoconstrictive response in stem villous arteries from heavy smokers than in those from nonsmokers (P <.05). CONCLUSION: Stem villous arteries of heavy smokers have altered mechanical properties and a greater vasoconstrictive response to endothelin 1 than do those from nonsmokers. These changes may compromise fetal placental blood flow and thereby contribute to the lower birth weights seen among infants born to heavy smokers.