We created experimental Staphylococcus epidermidis endophthalmitis of moderate severity in the aphakic rabbit eye by injecting 100,000 organisms of a standardized laboratory strain (ATCC 155) into the mid-vitreous cavity. This model of endophthalmitis self-sterilizes in about 4 days, but inflammatory signs continue to increase 5 to 7 days after the initial bacterial inoculum. Control eyes were compared with eyes treated with five different strategies 24 hours after bacterial inoculation: intravitreal cefazolin sodium, intravitreal cefazolin plus intramuscular corticosteroid, vitrectomy plus intravitreal antibiotics, vitrectomy plus intravitreal antibiotics and intramuscular corticosteroids, and vitrectomy plus intravitreal antibiotics and corticosteroids. Quantitative grading of inflammation and media clarity were compared at the end of weeks 1, 2, and 3 after treatment. At week 1, eyes treated with vitrectomy had significantly lower inflammatory scores; those treated with corticosteroids had significantly lower scores than those without. The two effects were independent. The best results were observed with treatment consisting of vitrectomy, intraocular antibiotics, and corticosteroids. This strategy also produced significantly more eyes with clear media at the end of week 3 than treatment with intravitreal antibiotics alone.