Previous research into the causes of allergic diseases was mostly focussed on potential risk factors in the environment, with little success, however. Over the past 10 years, focus has therefore more been directed against protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. The composition of the microflora differs between healthy and allergic infants and in countries with a high and low prevalence of allergies. These differences are apparent within the first week of life, or even in the maternal vaginal flora during pregnancy and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Prospective intervention studies, in which the gut flora was modified from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.