A systematic study was made to measure the generation of defective interfering particles upon up to 13 serial passages of two measles vaccine strains, Edmonston and Edmonston-Zagreb, through either simian (Vero) or human (WI-38) cell lines. Results for the Vero cell passage were nearly identical for both viruses. Infectivity titers dropped by nearly 8 logs to undetectable levels at passage 4 and cycled between maximum and minimum levels every 4 passages. Samples with the lowest infectivity titers produced the greatest reduction in titer of standard virus and contained an approximately 900-nucleotide subgenomic RNA for the Edmonston strain and two subgenomic RNAs of 4300 and 3000 nucleotides for the Edmonston-Zagreb vaccine strain. A defective interfering RNA-specific reverse transcription-polymerase chain reaction (RT-PCR) detected subgenomic RNAs at all passage levels. In contrast, samples obtained after passage of these viruses in WI-38 did not reduce the yield of standard virus and did not contain subgenomic RNAs in both Northern blot and RT-PCR assays. These results clearly show that cell type rather than virus strain affects defective interfering particle generation for measles virus.