While most coagulase-negative Staphylococcus (CNS) are apathogenic, recent evidence suggests some food and animal derived CNS isolates may carry and express virulence factors including classical enterotoxins, toxic shock syndrome, and methicillin resistance genes. The present study was designed to assess the potential role of CNS in the epidemiology of foodborne illnesses and to determine the likelihood of food and domestic animals as transmission vehicles of methicillin resistance. Of the animal-derived food samples tested, 27.3% (39/143) were Staphylococcus-positive compared to only 9.5% (23/242) of the plant foods. A total of 92 Staphylococcus spp cultured from 385 food (62/92) and 30 diagnostic animal (30/92) samples were tested by the polymerase chain reaction (PCR) for classical enterotoxin (sea, seb, sec, sec/, and see), toxic shock syndrome toxin-1 (tsst-1), and mecA genes. All PCR-positive isolates were further tested by immunoblotting for production of the corresponding toxin. Susceptibility patterns of both CNS and coagulase-positive Staphylococcus (CPS) were assessed for ~- lactam antimicrobial agents and the isolates analyzed for presence of the mecA gene. Of all study isolates, 20/92 (21.7%) were CPS and 72/92 (78.3%) CNS. Of the 20 CPS isolates, 15.4% (2/13) 5. aureus cultured from steak were sec positive while only 1/7 (14.3%) CPS (5. aureus) from a diagnostic feline sample was positive for both sec and tsst-1 genes. Both toxigenic 5. aureus isolates from steak and a diagnostic feline sample also expressed detectable amounts of SEC and TSST-1 toxins. On the other hand, 1.4% (1/49) of the CNS (5. lugdunensis) from strawberries was positive for the sec gene but negative for SEC toxin and 2/49 (2.8%) of the CNS (5. hominis) gave unexpected base pair PCR products with see primers. All CNS isolates were generally susceptible to test ~-lactam antimicrobial agents; 80% of the CPS isolates were resistant to penicillin and amoxicillin of which 1/20 (5%) were positive for the mecA gene. Based on this data, 3/20 (15%) of CPS and 3/72 (4.2%) of CNS isolates were positive for toxigenic genes thus underscoring the potential role food-derived CNS isolates may have in the epidemiology of foodborne illnesses. Although only 5% of the CPS and none of the study CNS isolates expressed mecA gene, 80% of the CPS were resistant to penicillin, suggesting other mechanisms of drug resistance. The presence of mecApositive CPS and toxin producing Staphylococcus isolates underscore the public health significance of organisms from this genus.