The present report-describes serologic data from five individuals without infectious mononucleosis (IM) who had very high levels of horse red blood cell agglutinins (1:896-1:7168) that were unusual in that they were minimally absorbed by either guinea pig kidney or beef red blood cell suspensions. Agglutination of sheep red blood cells was negative, and Epstein-Barr virus (EBV)-specific serodiagnostic tests revealed evidence for long past primary infections. In one of the five cases, serologic findings suggested a more than usually active EBV carrier state, as evident from persistently high anti-VCA (IgG) levels of 1:1280 and the continual presence of anti-R at 1:40. Sera from all cases predictably interfered with several commercially available IM-specific rapid slide agglutination tests. The incidence of such findings was estimated to be no more than one per one thousand non-IM cases. In three patients adequately studied, the poorly absorbable horse agglutinins persisted in serum samples over periods of five to nine years. The significance of these findings is discussed.