Damselfish ileurofibromatosis (DNF) is a neoplastic disease affecting the peripheral nervous system and chromatophores of bicolor damselfish Pornacentruspartitus on Florida (USA) reefs. This report presents the results of transmission experiments using intramuscular and intraperitoneal injection of a variety of tumor preparations to induce DNF. Neurofibromas developed within 1 yr of injection in 76% of fish injected with homogenates of spontaneously occurring tumors with earliest tumor development occurring at 5 to 6 wk post-injection. Cell-free transmission using 0.2 pm filtrates of DNF tumor homogenates was observed, demonstrating that the agent responsible for DNF is subcellular. Four out of five tumor cell lines established from neurofibromas were found to be tumorigenic when injected, while cells cultured from normal fish had no effect, indicating that the etiologic agent of DNF was present and infectious in tumor cell lines but not in cell lines or primary cultures derived from healthy fish. Serial passages of tumors were conducted through 19 passage generations in vivo. A comparison of the cumulative time to tumor distributions showed that most experiments beyond the third serial passage yielded significantly faster tumor development than was obtained by passaging from spontaneous tumors. Induced tumors exhibited more localized growth patterns and were typically more rapidly g]-owing and more rapidly lethal than spontaneous tumors. In contrast to the differences in growth patterns observed, the histological phenotype of the spontaneous, wild-type DNF lesions was indistinguishable from that of the induced tumors obtained from serial passages as well as in experiments involv~ng cell-free filtrates and cultured tumor cells. These observations indicate that the process of neoplastic transformation is relatively stable in this system, \nth little or no phenotypic drift caused by these manipulations. Naturally occurring, transmissible cancers that arise from cells of the central or peripheral nervous system or from chromatophores have not been previously identified. Thus, DNF is a unique disease and may provide an important model for investigating thls rather unique form of viral oncogenesis.