Quantitative microfluorimetric measurements on individual acridine orange (AO) stained cells showed that leukocytes from patients with infectious mononucleosis (IM) exhibited considerably greater AO binding to deoxyribonucleoprotein (DNP) than leukocytes from healthy persons. The higher binding of AO could not be explained by an increase in the amount of DNP in IM cells but by an increased number of binding sites in DNP accessible to AO. This was the result of structural changes in the DNP complex of the IM cells, possibly due to weakened bonds between the DNA and protein moieties of DNP. The binding of AO to IM leukocytes was highest in the early phase of the disease and usually normalized after recovery. However, an increased AO binding of leukocytes from patients after recovery was frequently observed when these cells were exposed to plasma from patients in the acute phase of IM.