Since hepatobiliary imaging with 99mTc=labeled iminodiacetic acid derivatives (HIDA) allows relatively separate, sequential measurement of hepatocyte clearance, parenchymal transit, and biliary excretion, these agents should be useful in differentiating intrahepatic cholestasis (IC) from other hepatobiliary disorders. We studied 18 patients with clinical evidence of IC in whom the parenchymal transit time was increased disproportionately to any decrease in hepatocyte clearance. In a second group of 14 patients with hepatocyte disease but without clinical evidence of IC, the average parenchymal transit time was increased less in relation to the average decrease in hepatocyte clearance than in the IC group. In 15 patients with extrahepatic biliary obstruction, the average hepatocyte clearance was disproportionately increased, as in IC, but large-duct obstruction was identified by scintigrams, ultrasound, or computed tomography. These preliminary results suggest that IC can be diagnosed with hepatobiliary imaging.