The p125 (p54/p80) coding region of two cytopathic (CP) strains (Oregon and Singer) and two noncytopathic (NCP) strains (NY-1 and Draper) of bovine viral diarrhea virus (BVDV) were amplified by the polymerase chain reaction, cloned and sequenced. The sequence data confirmed that the two CP strains do not possess any insertion or deletion in their p125 gene as observed in many other CP strains. In the p80, which showed a high amino acid sequence homology among all strains, no amino acid substitution should could be found which distinguished these CP strains from the NCP strains NY-1 and SD-1. Many amino acid substitutions were found in p54 but their individual importance in the CP phenotype is not clear since critical domains of p54 have not yet been experimentally defined. The p54 protein is much less conserved than p80, and sequence homology, as well as dendrogram analysis, permitted us to distinguish two genotypic groups of BVDV (Ia and Ib). The mean homology between strains of these two groups was 77.3/80.4% for the nucleic acid/amino acid sequences while it was 88.0/88.8% and 91.6/93.3% within groups Ia and Ib, respectively. Furthermore, we found that the p125 sequence of our NY-1 strain showed only 92% sequence homology with the partial p80 gene reported for NY-1 but 99.8% homology with another partial sequence of the p125 gene of NY-1 reported elsewhere. These observations underscored the difficulty of maintaining a specific BVDV strain, especially the NCP biotype, in cell cultures.