Passage history of the FMDV populations employed in the present study. Filled squares and rectangles represent biological and molecular clones, respectively; empty circles represent uncloned viral populations. In lineage 1 FMDV clone C-S8c1 was subjected to 22 serial plaque transfers to obtain clone C229 (17). Then it was subjected to 50 serial infections in BHK-21 cells, as detailed in Materials and Methods. At passage 50 the population was subjected to molecular and biological cloning and individual clones were analyzed by nucleotide sequencing. In lineage 2, FMDV clone C-S8c1 was passaged 100 times in BHK-21 cells (27, 31), as detailed in Materials and Methods. At passage 50 the population was analyzed by molecular cloning and nucleotide sequencing. At passage 100, a MAb SD6-resistant mutant was obtained (RED). Triplicate samples of this virus were serially passaged 25 times at a multiplicity of infection of 0.1 PFU per cell (4 × 106 cells infected with 4 × 105 PFU of virus). RNAs from individual biological clones from these populations were analyzed by nucleotide sequencing.