We report on three cases of severe disseminated Herpes simplex type-2 (HSV-2) infection that occurred in two orthotopic liver-transplant (OLT) and one renal-transplant patients. In two cases, i.e., in the OLT patients, this was associated with HSV-2-related acute hepatitis. The rapid onset of IV acyclovir (ACV) therapy led to recovery within 8-12 days. Although rare, HSV-2-disseminated infection, in the context of organ transplantation may be life-threatening, but can be cured if ACV therapy is initiated early in the course of this disease.