The spectrum of activity of fosfomycin and its pharmacological behaviour make it an attractive candidate for the oral treatment of uncomplicated urinary tract infection. Various factors affect the antibacterial activity so that results in different culture media vary widely. The highest activity was displayed in Eugonbroth and such results correlated well with those obtained in pooled human urine. The activity was enhanced in acid conditions such as commonly exist in infected urine. Glucose-6-phosphate potentiated the activity of fosfomycin against Escherichia coli and some other bacteria when tested in Eugonbroth (but less predictably in human urine) and the potentiating effect may be necessary in order to obtain therapeutically meaningful results in susceptibility tests. Experiments in an in vitro model of the treatment of bacterial cystitis (carried out in the absence of glucose-6-phosphate) indicated that both sensitive and ‘resistant’ strains of E. coli respond to concentrations of fosfomycin achievable by high-dose oral therapy with the trometamol salt. Resistance did not emerge in previously sensitive strains (or in one of the 2‘resistant’ strains), providing a high peak level of antibiotic was achieved.