Four patients are described who have manifested unusual reactions to combined irradiation and chemotherapy when irradiation of the liver was involved. Two had had partial resection of the liver and irradiation of all of the remaining liver tissue; each of the others, with an intact liver, may have had compromise of liver function by infection and/or by lower dose irradiation of the left lobe of liver. We suggest that irradiation of the liver, especially in patients who receive chemotherapeutic agents which may require liver for detoxification or excretion, be very carefully administered, even at a minimal dose. Any underlying compromise of the liver must be evaluated carefully. In each patient, hemoglobin levels were normal throughout the clinical course.