Straus, S E, Dale, J K, Tobi, M et al. · The New England journal of medicine · 1988 · DOI
Researchers tested whether acyclovir, an antiviral drug, could help people with ME/CFS who had signs of past Epstein-Barr virus infection. In this carefully controlled study of 27 patients, about half received the real drug and half received a placebo (fake treatment). After 37 days of treatment, similar numbers of people felt better in both groups—suggesting the drug itself wasn't the reason for improvement.
This study addresses a historically important hypothesis—that ME/CFS might result from persistent EBV infection amenable to antiviral therapy. As one of the first rigorous trials to evaluate this mechanism, it provides evidence that targeting EBV alone is insufficient and helps redirect research toward other pathophysiological mechanisms in ME/CFS.
This study does not prove that EBV plays no role in ME/CFS pathogenesis, only that acyclovir treatment does not improve symptoms in patients with abnormal EBV serology. It also does not establish whether different dosing regimens, patient subgroups, or earlier intervention might have different effects. The correlation between improvement and mood suggests subjective reporting bias rather than ruling out biological mechanisms entirely.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Straus, S E, Dale, J K, Tobi, M, Lawley, T, Preble, O, Blaese, R M, et al. (1988). Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.. The New England journal of medicine. https://doi.org/10.1056/NEJM198812293192602
BibTeX
@article{mecfsatlas-straus-1988-acyclovir-treatment,
author = {Straus, S E and Dale, J K and Tobi, M and Lawley, T and Preble, O and Blaese, R M and Hallahan, C and Henle, W},
title = {Acyclovir treatment of the chronic fatigue syndrome. Lack of efficacy in a placebo-controlled trial.},
journal = {The New England journal of medicine},
year = {1988},
doi = {10.1056/NEJM198812293192602},
note = {PubMed: 2849717},
url = {https://www.mecfsatlas.com/evidence/straus-1988-acyclovir-treatment},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/straus-1988-acyclovir-treatment
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