Four woodchucks chronically infected with hepatitis delta virus (HDV) were treated with cyclosporin-A (CyA) for 11 weeks. All animals had detectable HDAg in the liver and two of them were also positive for HDAg and HDV-RNA in serum. Reappearance of HDV in serum was noted in one of the two non-viraemic animals and increased viraemia in the two viraemic. HDV-RNA levels became elevated within a week of starting treatment and an inverse relationship between HDV-RNA and WHV-DNA became apparent during the treatment period. With discontinuation of treatment, HDV-RNA levels either returned to pretreatment levels or became negative. The remaining animal showed no return of viraemia during CyA treatment; HDV-RNA remained negative and WHV-DNA levels did not change. Liver biopsies revealed a slight increase in lobular activity during CyA treatment in the animals showing increased viraemia. These data are consistent with the hypothesis that the host immune response exerts a negative control on the level of HDV viraemia and that HDV influences HBV replication independently of the host immune response. In an animal that may have been clearing HDV, immunosuppression did not result in recurrence of viraemia.