Three patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during the course of disseminated Herpes Varicella-Zoster (HVZ) virus infections are reported. In one patient and two previously reported patients, SIADH occurred at or shortly after admission, prior to antiviral drug therapy. In two patients and one previously reported patient, SIADH began or hyponatremia worsened after vidarabine therapy was begun. Therefore, SIADH may occur during the course of untreated, disseminated HVZ infection. However, the relatively high fluid volume required to dilute vidarabine may play a role in the development of the clinical and laboratory manifestations of SIADH, in patients receiving the drug. Physicians should avoid excess fluid intake and monitor serum sodium carefully when caring for patients with disseminated HVZ infections. Doses of vidarabine greater than 10 mg/kg/day may increase the likelihood of SIADH. Acyclovir therapy was not associated with worsening of hypotonic hyponatremia in our patients.