We investigated cefoperazone, a new third generation cephalosporin, for its possible use against bacterial eye infections. One hundred eighty strains of bacterial isolates of ocular significance were subjected toin vitrotesting. Excellent results were noted, with only two species,Streptococcus faecalisandAcinetobacter anitratus, showing resistance. Minimum inhibitory concentration determinations were done on a few strains ofStreptococcus aureus.All strains ofS. pneumoniaeandS. viridanswere highly sensitive. S.aureusstrains were moderately sensitive. Four strains ofPseudomonas aeruginosawere testedin vitrofor synergy with a combination of cefoperazone and tobramycin using a two-dimensional checkerboard titration procedure. Two strains showed synergy and two were equivocal. Anin vivotreatment study was done on 28 rabbits with a pseudomonas ulcerative keratitis. The animals were treated with cefoperazone alone, tobramycin alone, or a combination of the two drugs. Control rabbits were treated with saline. When the corneas were excised and cultured, the combined therapy resulted in fewer colonies than when cefoperazone or tobramycin were used alone; the differences were not significant for tobramycin, although they were significant for cefoperazone. Clinical evaluation showed that the combined therapy was significantly more effective than either antibiotic used alone.