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Symptomatic infection developed in 16 of the 45 untreated bacteriuric women (36%). Loin pain and fever developed in onlv two of these subjects, whereas in the remainder the symptoms were frequency and dysuria. Comparison of these findings with the natural history of asymptomatic significant bacteriuria in pregnancy shows that the total incidence of symptomatic infection is similar. The distinguishing feature between the natural history of asymptomatic significant bacteriuria in pregnant and non-pregnant women is the severity of symptoms. Asscher et a!. (1966) showed that in pregnancy the urine is continuously maintained at optimal pH for the growth of urinary pathogens. It may be that the greater severity of symptomatic infections arising in pregnant bacteriuric women is related to this.A single course of treatment initially cured bacteriuria in 80 U, of cases, but was soon followed by relapses and reinfections, particularly in women who had been shown to have radiological abnormalities. One year after treatment, therefore, the cure rates among treated and untreated bacteriuric subjects no longer showed a significant difference. Not surprisingly, therefore, treatment failed to prevent the development of symptoms of overt infection. Moreover, it has been shown that the reinfections which followed treatment were more commonly associated with the development of symptoms than the persistent or relapsing infections in the untreated or unsuccessfully treated subjects. This would suggest that bacteriuric women may have developed tolerance to the particular organism harboured in their urinary tract and that treatment can temporarily upset this equilibrium. The occurrence of tolerance to the pyrogenic substances of Gram-negative bacteria in animals and humans with urinary tract infections has been demonstrated by McCabe (1963) and may explain the more frequent development of symptoms in subjects who are reinfected after treatment.Our observations suggest that a search for significant bacteriuria in non-pregnant female populations does not satisfy either of the principal requirements of a good screening procedure. In many instances it fails to detect urinary tract infection at an early and reversible stage of its natural history (Sussman et al., 1969), and treatment suitable for use on a large scale fails to alter its natural history. The present study still leaves an important gap in our understanding of the clinical significance of bacteriuria-namely, its relationship to the ultimate development of scarring and contraction of the kidneys and of renal failure. It is hoped that long-term follow-up of the bacteriuric and control subjects of this study will help us to provide an answer. At present it seems likely that even if persistent bacteriuria did lead to progressive renal damage its eradication would be difficult, costly, time-consuming, and probably hazardous.

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