The incidence of trimethoprim-resistant Enterobacteriaceae has not increased since the introduction of the combination trimethoprim-sulfamethoxazole (TMP-SMX) into the clinical use at our centre in 1973. Using the minimum inhibitory concentration (MIC) as the index of trimethoprim resistance, this ranged from 1.6 to 800 mug/ml; for the majority of isolates it lay between 1.6 and 12.5 mug/ml. About half of these trimethoprim-resistant organisms were sensitive to sulfonamide. In vitro data suggest that organisms resistant to sulfonamide as well as to trimethoprim, where the MIC for the former drug is 3.1 mug/ml or less, will be susceptible to the combination. More resistant organisms, i.e., those for which the MIC of trimethoprim is 6.2 mug/ml or more, often appear quite resistent to the combination. There is no evidence that previous therapy with TMP-SMX is a significant predisposing factor to infection with these organisms, although there is a significant correlation between previous TMP-SMX therapy and infection with organisms with a high level of trimethoprim resistance. Organisms harbouring R-factor resistance or thymine-dependent mutants were not encountered during the course of this study.