Biliary disease, primarily manifesting as papillary stenosis or sclerosing cholangitis, is being increasingly recognized as a problem in the acquired immunodeficiency syndrome (AIDS) and may be amenable to specific treatment. Ultrasound, followed by endoscopic retrograde cholangiopancreatography (ERCP) for definitive diagnosis, is currently the prime mode of investigation of suspected hepatobiliary diseases in AIDS. There are few published reports of the use of radionuclide cholescintigraphy in the assessment of these patients. This report presents Tc-99m DISIDA cholescintigraphy data from three patients with AIDS-related hepatobiliary disease confirmed by ERCP. Radionuclide cholescintigraphy was abnormal in all three patients. In two of the subjects, there was focal duct dilation with strictures in the biliary tree. The third patient demonstrated diffuse hepatic parenchymal retention with marked delay in tracer washout. Two of the subjects, treated with specific anticryptosporidial therapy, subsequently underwent progress cholescintigraphy. In one of these patients with initial diffuse parenchymal retention, there was marked improvement in scan appearances. The second patient with initial duct dilation had no significant change in scan appearances, but quantitative analysis did demonstrate improvement in hepatobiliary tracer clearance rate. In conclusion, although ERCP remains the gold standard in the diagnosis of AIDS-related biliary disease, radionuclide cholescintigraphy may be a useful modality in these patients as a screening test before proceeding to more expensive and invasive techniques. In addition, quantitative analysis of cholescintigraphy may allow assessment of patient response to specific antimicrobial or surgical intervention.