Although various stressors appear to influence herpesvirus infections, the underlying mechanisms have not been studied. A prospective design was used to examine the effects of examination stress and loneliness on the transformation of B lymphocytes in mixed cultures of T and B lymphocytes by Epstein-Barr virus (EBV). Three blood samples were drawn from 42 EBV-seropositive medical students, with the baseline sample taken 1 month before their final examinations, the stress sample drawn on the first day of final examinations, and the third sample taken the first week after their return from summer vacation. A median split on the UCLA Loneliness Scale divided the subjects into high- and low-scoring loneliness groups. There were significant effects for change over trials, with the lowest transformation levels (i.e., more virus required to transform cells) found in the stress sample. There was also a significant main effect for loneliness, in which high loneliness was associated with lower transformation levels. Possible immunological pathways for the observed changes are discussed.