Response of rodents to experimentally induced subcutaneous infection was examined to determine whether laboratory rats used in invasive procedures have a superior ability to withstand wound infection than do hamsters and mice. Rats, hamsters, and mice were injected subcutaneously with 10(9), 10(7), and 10(5) colony-forming units of Staphylococcus aureus. Quantitative counts of viable S aureus from the injection site, bacteriologic cultures of heart blood, and histologic examinations of the subcutaneous tissues were performed. Multiple linear regression of the quantitative data and equality of regression lines among groups were determined. Results indicated that the ability to eliminate bacteria varied between species and depended on the dose injected within each species. Compared with hamsters and mice at all doses, rats eliminated bacteria faster and had the mildest and most rapidly organized inflammatory response after inoculation. Experimental bacteremia developed in 3.7% of all animals evaluated, with no species-specific pattern. The rat was more resistant to localized wound infection with S aureus than were hamsters and mice.