The purpose of this study was to find a "threshold" quantity of organisms (i.e. inoculum) to produce clinical endophthalmitis and determine the natural course of intravitreal bacterial counts following inoculation in a rabbit model of Staphylococcus epidermidis endophthalmitis. S. epidermidis endophthalmitis was induced experimentally in 18 New Zealand white rabbits. Eyes were injected with 2.0 x 10(3) (Group I: n = 3), 2.0 x 10(4) (Group II: n = 3), 3.0 x 10(5) (Group III: n = 3), 3.0 x 10(6) (Group IV: n = 3), 3.0 x 10(7) (Group V: n = 3), or 3.0 x 10(8) (Group VI: n = 3) organisms. Serial quantitative bacterial cultures (colony counts) were performed on the vitreous every eight hours for 9 days. All eyes in Groups I and II became culture negative by 24-64 hours post-inoculation (PI). All eyes in Groups III-VI remained culture positive [approximately 600-4000 colony forming units (CFU) per cm3] at 48 to 72 hours PI and were stable for the remainder of the nine day study period. Previous work suggests that the host's inflammatory response is more important than had been recognized. Previous rabbit models of infectious endophthalmitis are known to become culture negative ("autosterilized") despite continued intraocular inflammation. This rabbit model demonstrates a "threshold" of infection where the host's immune response is overwhelmed and "autosterilization" does not occur. When inoculated with 3.0 x 10(5) or greater S. epidermidis organisms of this strain, continued active bacterial replication can now be studied in the rabbit.