The effect of furosemide on vascular smooth muscle was studied on segments of rabbit blood vessels. Furosemide (20 micrograms/ml) induced small (3-4%) decreases in resting tension whereas nitroglycerin (0.5 micrograms/ml) induced decreases from 8 to 13%. The addition of albumin (45 g/l) abolished the furosemide response whereas the nitroglycerin response was unaffected. Similarly the pronounced effect of nitroglycerin on electrically evoked contractions was unaffected by the presence of albumin whereas the furosemide effect was weakened by albumin. The biologically determined free fraction of furosemide increased with increasing drug concentrations from 13% at 16 micrograms/ml to 35% at 256 micrograms/ml.