A two-day-old Standardbred filly was examined for progressive lethargy and weakness of eight hours duration. Signs of recumbency, depression, pale mucous membranes, icterus and tachycardia suggested a diagnosis of neonatal isoerythrolysis. Laboratory findings supported this diagnosis, and medical therapy, including blood transfusions, fluids, antibiotics and oxygen therapy resulted in marked clinical improvement. This condition, which is relatively uncommon in horses, can have fatal consequences if not treated early enough. Early recognition and treatment, as in this case, can prevent mortality. Predictive testing and post-partum management can also prevent deaths due to isoerythrolysis. These will be discussed in this report.