Trimethoprim-resistant gram-negative bacilli have been isolated since shortly after the combination of a sulfonamide with trimethoprim available for clinical use 10 years ago. Factors not yet fully understood are responsible for the high or low percentage of resistant strains isolated in different countries at different times. Despite the widespread use of this combination, the percentage of trimethoprim-resistant bacteria has not exceeded 25% in a general hospital in Paris. Resistance to trimethoprim can be mediated by mutations within the bacterial chromosome or can be plasmid-mediated.