We describe a method for detecting virus-specific RNA sequences using a nonradioactive enzyme system, and analyze coxsackie B4 virus (cox. B4) RNA sequences in infected mouse kidney with pathological changes. Diffuse mesangial proliferation was observed transiently 24 h after inoculation of cox. B4 virus in glomeruli. OCT-treated thin sections of the same tissue were hybridized in situ using a digoxigenin-labeled oligonucleotide probe. The strongest signal was observed in the mesangial sample. These findings suggest that the transient proliferative mesangial changes were caused by direct injury following virus infection without immune complex.