CASE REPORT: . BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an immune activation syndrome arising either as a primary form of heritable gene mutations or induced secondarily by immune insult, such as autoimmune disease or viral illness, most commonly EBV. Here we compare two unrelated cases of EBV associated HLH, admitted to our institution in a single month.Patient A is a previously healthy 5-year-old female who presented with 7 days of fever, fatigue, oral lesions, and splenomegaly.Patient B is a previously healthy 15-month-old female who presented with 4 days of fever, fatigue, significant lymphadenopathy, and hepatosplenomegaly. DISCUSSION: The general reported incidence of HLH is 1.2 cases per 1,000,000 individuals per year. Despite this rare prevalence, there has been 4 paediatric EBV associated HLH cases in our hospital in the past year. The 2 cases reported above have been diagnosed in the past month.Both patients have started treatment per HLH-2004 protocol. 2 of the 4 patients are of Native American ethnicity.The main questions to be raised by this observation is the possibility of an EBV strain endemic to the area, that could have triggered a significant immune response culminating in HLH. The other question is the possibility of a yet undefined genetic association or underlying biology specific to a certain population or ethnic group in New Mexico.(Table is included in full-text article.)