In ten experiments, 53 castrated male 4- to 8-week-old weanling pigs were given adriamycin (ADR) IV at mean dosages of 0.64, 1.0, 1.6, 3.2, or 6.4 mg/kg/week at various frequencies for up to 20 weeks. Mortalities in pigs given these dosages were 0% after 112 days, 100% after 134 days (survival time was 48 to 134 days), 91% after 75 days (survival time was 5 to 75 days), 100% after 28 days (survival time was 23 to 28 days), and 100% after 14 days (survival time was 10 to 14 days), respectively. Survival time was prolonged in younger pigs and in pigs given smaller but more frequent dosages of ADR. Characteristic gross and histopathologic alterations of ADR toxicosis were observed in pigs given 1.0, 1.6, 3.2, or 6.4 mg/kg/week mean dosages. The most frequent lesions were in the alimentary tract, myeloid and lymphoid tissues, skin, and perivascular tissues at injection sites. Alimentary tract lesions were mucosal epithelial atrophy, with secondary fibrinonecrotic inflammation in the oral cavity and large intestine. Marked hypoplasia was seen in bone marrow and lymphoid tissues, with frequent terminal hemorrhagic diathesis and septicemia. Several days before death, the pigs developed severe dermatitis over the ventral portion of the abdomen and inner surfaces of the limbs. Perivascular necrosis and cellulitis produced by extravasation of ADR was a frequent complication of treatment. Terminal severe acute pneumonia occurred in most pigs. Pericarditis or cardiomyopathy (or both) developed in 14 pigs, given 0.64, 1.0, or 1.6 mg/kg each week (mean cumulative dosage 520.5 mg/m2 of body surface). Characteristic histopathologic and ultrastructural alterations in affected cardiac muscle cells were vacuolar degeneration, myocytolysis, and hyaline necrosis. Nephrotoxicosis also was in pigs with chronic ADR toxicosis. Systemic antibiotic treatment did not prolong survival of ADR-treated pigs in two experiments, but did in one other experiment.