From brain samples collected from domestic animals in Ethiopia, two rabies-related viruses were isolated. According to their reactivity pattern with anti-nucleocapsid monoclonal antibodies, they were characterized as Lagos bat virus (isolate Eth-58) and Mokola virus (isolate Eth-16). This classification was confirmed by neutralization experiments with Mokola and Lagos bat specific antisera. Two potent anti-rabies vaccines were unable to protect mice against the two rabies-related viruses. In order to investigate molecular relationships to classical rabies virus, cDNA cloning and sequencing was performed. The RNA genome of both viruses comprises 12 kilobases (kb) and has an organization similar to that of rabies virus with the gene order 3'-N-P-M-G-L-5'. Using virus-specific cDNA as probes in heterologous hybridization experiments, the RNAs of other members of lyssavirus serotypes 2 and 3 were detected. From hybridization experiments and sequence analysis of the 3' terminal 5,5 kb of the genomes, Eth-16 and Eth-58 viruses were shown to be equally genetically distant from rabies virus with 60% nucleotide identity; Eth-16 and Eth-58 had 68% homology.