Abrabinosyl-N6-hydroxyadenine (ara-HA) was tested for its antiherpesvirus and immunosuppressive activities in vivo and in vitro. Mouse strains were used that had been shown earlier to be very susceptible to intraperitoneal (i.p.) or intracerebral (i.c.) inoculation of a virulent strain of herpes simplex virus Type 1 (HSV-1). Susceptible mice were inoculated i.p. or i.c. with a stock pool of HSV-1 and treated with ara-HA (i.p.) beginning at least 24 hr later. The mice were given a 10-day course of drugs and followed for at least 21 days. Similar experiments were carried out with ara-A for comparative purposes. Ara-HA was found to protect mice inoculated with HSV-1 significantly better than ara-A. Lower concentrations of drugs were required and a higher percentage survived. Later challenge of the ara-HA-treated mice with HSV-1 demonstrated that these mice had become immune to HSV-1, indicating that the immune system is not severely affected by this course of ara-HA. A 10-day course of ara-HA, which was found to protect mice from 100 LD50 of HSV-1, reduced the capacity of the mouse lymphocytes to respond to allogeneic cells only slightly. In vitro ara-HA inhibited HSV-1 replication as well as proliferation of lymphocytes exposed to mitogen.