From january 1972 to december 1981, nearly 54.000 strains of enterobacteria isolated from clinical specimens were tested for susceptibility to the trimethoprim-sulfamide combination (co-trimoxazole). During that period, the overall resistance to trimethoprim increased from 17.9% to 32.7%, and there was a fourfold increase in the number of strains exhibiting high level resistance; 246 trimethoprim-resistant plasmids were transferred into E. coli K 12. The number and frequency of the other resistance markers co-transferred with trimethoprim are constantly increasing and as a result, more and more antibiotics are likely to be responsible for the selection of trimethoprim-resistant plasmids. In contrast, the proportion of trimethoprim-resistant mutants decreased from 11% to 5%. The use of co-trimoxazole in France may explain this low incidence.