• The effectiveness of cryotherapy alone and in combination with topical tobramycin sulfate therapy for experimental Pseudomonas keratitis was determined in guinea pigs and rabbits. Results were evaluated quantitatively by determining numbers of viable bacteria surviving in corneas. A brass probe cooled to—79 °C and applied directly to infected corneas for six seconds resulted in an immediate 99.9% reduction in bacteria. One freeze-thaw cycle followed by topical tobramycin therapy was significantly more effective than tobramycin therapy alone in five of six strains tested. None of the corneas treated with tobramycin alone demonstrated no growth, whereas 24 of 42 of these infected corneas showed no growth after the combination treatment. We conclude that cryotherapy alone had a rapid bactericidal effect on experimental Pseudomonas keratitis and that it significantly potentiated topical antibiotic therapy for most strains.