Aims: To predict and validate survival of non-acid adapted Escherichia coli O157 in an environment mimicking the human stomach. Methods and Results: Survival was predicted mathematically from inactivation rates at various, but constant pH values. Predictions were subsequently validated experimentally in a pH-controlled fermentor. Contrary to prediction, acid-sensitive cultures of E. coli O157 survived for a long period of time and died as rapidly as acid-resistant cultures. Experimental results showed that in an environment with changing pH, acid-sensitive cultures became acid-resistant within 17 min. Cyclo fatty acids was reported to be a factor in acid resistance. As synthesis of cyclo fatty acids does not require de novo enzyme synthesis and thus requires little time to develop, we analysed the membrane fatty acid composition of E. coli O157 during adaptation. No changes in membrane fatty acid composition were observed. Conclusions: Acid adaptation of E. coli O157 can occur during passage of the human gastric acid barrier, which can take up to 4 h. Significance and Impact of the Study: The ability of acid-adapted bacteria to survive the human stomach is an important virulence factor. The ability of non-acid adapted E. coli O157 to adapt within a very short period of time under extreme conditions further contributes to the virulence of E. coli O157.