An experimental model of staphylococcal keratitis in guinea pigs was devised that is suitable for quantitative evaluation of therapy. The growth curve in the cornea of a virulent strain of Staphylococcus aureus was determined. The organism multiplied rapidly, reached a peak in about 12 hours, and began to decline in numbers after three days. Infections were relatively resistant to therapy begun 24 hours after infection was established. Treatment started earlier when fewer bacteria were present was more effective than treatment begun later. Treatment begun at the time of infection, which might be considered prophylaxis, was highly effective. When treatment was begun eight hours after infection, tobramycin sulfate and gentamicin sulfate solutions administered topically in doses of 20 mg/ml were more effective than topical bacitracin, erythromycin, clindamycin phosphate, or a solution containing polymyxin B sulfate, neomycin sulfate, and gramicidin. Bacitracin and erythromycin ointments were ineffective.