['Diltiazem reduces systemic blood pressure by decreasing the vascular smooth muscle tone. In the liver however, diltiazem seems to cause vasoconstriction, as evidenced by increases in portal pressure. The questions raised by this observation are concerned with a) the site of action of diltiazem (large vessels or sinusoids), b) the formation of permeability barriers and c) the role of Ca2+. The experiments in the present study should provide an answer to these questions.', 'The experimental system was the hemoglobin-free perfused rat liver. The multiple-indicator dilution technique was employed with simultaneous injection of [14C]sucrose and [3H]water. Mean transit times and distribution spaces were calculated from the normalized outflow profiles.', 'Calcium alone did not affect the hemodynamics of the liver. Diltiazem, however, changed several hemodynamic parameters when Ca2+ was present, but it was inactive in the absence of this cation. The hemodynamic effects of 500 microM diltiazem were: a) diminution of the transit time through the large vessels (t(o)) and, consequently, of the accessible vascular space (66.9%); b) diminution of the mean transit time of [14C]sucrose (tsuc) and, consequently, of the accessible sinusoidal space (28.1%); c) diminution of the mean transit time of tritiated water (twater) and, consequently, of the accessible cellular space (68.9%); d) diminution of the cellular to extracellular space ratio (theta) from 1.42 +/- 0.05 to 0.46 +/- 0.11.'] Are the hemodynamic effects of diltiazem in the isolated perfused rat liver Ca ( 2+ ) -dependent?