Fifty strains of Pseudomonas isolated from clinical material were tested in vitro for susceptibility to carbenicillin, gentamicin, and combinations of the two drugs. The combination of carbenicillin and gentamicin was shown to have a synergistic effect on 46 of the strains tested. For testing the synergistic effect of carbenicillin plus gentamicin in vivo, an experimental model of lethal pseudomonas infection was developed in the rat. Animals treated with saline, carbenicillin alone, or gentamicin alone experienced rapid multiplication of Pseudomonas at the site of bacterial challenge, severe bacteremia, and died within 24 hr. In contrast early combined therapy with carbenicillin plus gentamicin decreased the number of bacteria at the challenge site, reduced the level of bacteremia, and resulted in survival of the animals during treatment. The synergistic effect of combined carbenicillin-gentamicin therapy was lost when treatment was delayed. These studies clearly indicate a synergistic effect of carbenicillin-gentamicin therapy in vivo for serious infections with Pseudomonas, when these antibiotics are synergistic in vitro against the organism, and suggest that combined carbenicillin-gentamicin therapy may be useful for certain pseudomonas infections in man.