A review of 1,192 student medical records shows a prior history of tonsillectomy in 41 percent of a control group and 22 percent of an infectious mononucleosis group--a significant difference (p less than 0.01). Nine hundred eighty-nine Stanford University students (421 females, 568 males) who visited Cowell Student Health Center between April and September, 1973, comprise the control group. Two hundred three students with positive monospot tests and clinical mononucleosis diagnosed between June, 1968, and May, 1973, comprise the experimental group. The lower incidence of tonsillectomy in the infectious mononucleosis group implies that the tonsillar lymphoid tissue serves as a reservoir and possible replicating milieu for the Epstein-Barr virus. Prior tonsillectomy may reduce the possibility of contracting infectious mononucleosis.