This study investigated the growth and survival of Escherichia coli O157:H7 during the manufacture of pepperoni to determine whether a 5-log10-unit decline in numbers, as recommended by the U.S. Food Safety and Inspection Service (FSIS), could be achieved. A range of pepperoni formulations with variations in salt (2.5 to 4.8%) and sodium nitrite (100 to 400 ppm) levels, and with pH (4.4 to 5.6) adjusted by manipulation of dextrose concentrations were prepared. The batters produced were inoculated with E. coli O157:H7 380-94 at a level of approximately 6.70 log10 CFU/g; changes in pathogen numbers, pH, titratable acidity, and sodium nitrite concentrations were monitored during fermentation and drying. With the standard commercial formulation (i.e., 2.5% salt, 100 ppm sodium nitrite, pH 4.8) E. coli O157:H7 numbers declined by approximately 0.41 log10 CFU/g during fermentation and a further 0.43 log10 CFU/g during subsequent drying (7 days). A regression equation was fitted to the data which showed significantly (P < 0.001) greater reductions in pathogen numbers in samples with increased salt and sodium nitrite contents and lowered pH. However declines were in all cases less than the target reduction of 5 log10 CFU/g.