A study was made to elucidate the effect of host cells on the HANA protein of Sendai virus. Two strains of Sendai virus were isolated from an epidemic in an animal laboratory by inoculating the lung homogenate of a moribund mouse either into LLC-MK2 cells (Oh-L) or into the allantoic cavity of embryonated eggs (Oh-E). Oh-E agglutinated chicken red blood cells at 37 degrees (HA37+), while Oh-L did not (HA37-). When Oh-L was passaged in eggs, conversion of the HA37- virus to the HA37+ virus readily occurred. A single point mutation was recognized on the HANA protein of the HA37+ virus either at position 525 (Gln----Arg) or at position 198 (Leu----Phe). Hl test with monoclonal antibody revealed conformational changes around the receptor binding site. Neuraminidase activity was also affected by these mutations. The changes in these biological activities of the HANA protein seemed to allow the HA37+ virus to replicate in eggs. On the contrary, the HA37+ virus replicates as efficiently as the HA37- virus in LLC-MK2 cells and no reversion to the HA37- virus was observed. The overall results indicate that the passage of Sendai virus in eggs resulted in selection of viruses possessing a specific mutation on the HANA protein. The pneumopathogenicity in mice was not significantly different between the HA37- virus and the HA37+ virus, suggesting the existence of genes other than the HANA gene that determine mouse pathogenicity.