Composting is a popular means of treating organic wastes, and properly controlled composting can destroy the pathogenic microorganisms present in wastes for a human- and environment-friendly end product. Therefore, optimization of windrow composting of food waste, manure, and bulking agents was evaluated for maximum pathogen inactivation (Salmonella and E. coli O157:H7). Seasonal effects on reductions of Salmonella and E. coli O157:H7 according to the compost temperatures were studied (90 to 150 days). Fecal coliforms and fecal streptococcus were also monitored during composting. The most probable number (MPN) method was used for enumerating both indicator and pathogenic microorganisms. The results of this study indicated that seasonal differences caused significant effects on the peak temperatures and the duration of high thermophilic temperatures (>= 55 degrees C) of windrows. Winter conditions resulted in inconsistent inactivation of pathogenic microorganisms including regrowth to high values during several time intervals. The reduction levels of Salmonella spp. and E. coli O157:H7 ranged from initial ranges of 377-483 MPN/g to final ranges of 6-150 MPN/g in whiter and to <= 0.3 MPN/g in summer It was also observed that summer composting resulted in a better correlation (r(2) > 0.90) between the number of fecal coliforms and the pathogenic microorganisms (Salmonella spp. and E. coli O157:H7). Fecal streptococcus was only slightly reduced in the majority of the trials from 377-483 MPN/g to 221-514 MPN/g in winter and from 365-460 MPN/g to a range of 11-265 MPN/g in summer Extreme Vertices Mixture Design (EVMD) analysis suggested an optimum mixture as: 43.3% food waste, 28.3% manure, and 28.3% bulking agents. The performance of the optimum mixture has been validated, achieving a high level of inactivation of pathogens similar to that with previous trials, with good correlations of fecal coliforms to the pathogens of interest, but with a high resistance of fecal streptococcus to inactivation. It was concluded that the EVMD design was successful in optimizing mixture components for windrow composting in order to achieve maximum pathogen reduction.