A neoplastic disease that affects a common species of marine fish, the bicolor damselfish (Pomacentrus partitus), on Florida reefs consists of multiple, disseminated neurofibromas (including plexiform lesions), malignant schwannomas, and hyperpigmented epidermal lesions. Based on similarities to von Recklinghausen neurofibromatosis, we have termed this disease damselfish neurofibromatosis. Previous surveys of the prevalence of fish with damselfish neurofibromatosis on Florida reefs demonstrated a distribution pattern of cases consistent with what would be expected for an infectious disease. The transmissibility of damselfish neurofibromatosis was assessed by inoculations of homogenized tumor tissue s.c. and i.p. into healthy bicolor damselfish. This protocol resulted in the development of Schwann cell tumors, identical to the naturally occurring lesions, at the injection sites in approximately 84% of inoculated fish. These tumors appeared within an average of 5 mo of inoculation for juvenile fish and 14 mo for adults. Experimentally produced tumors appeared to arise in host fish by the neoplastic transformation of host nerves rather than by transplantation and proliferation of tumor cells from the donor fish. This finding suggests that an infectious, transmissible agent such as a virus may be the etiological agent responsible for production of neurofibromas and other Schwann cell tumors in this species of fish.