Severe flooding may become more frequent due to global warming. A historical cohort study was conducted by telephone interview for new episodes of illness in all age groups, and for psychological distress in adults, following severe river flooding on 12 October 2000 in the town of Lewes in Southern England. Two hundred and twenty-seven residents of 103 flooded households and 240 residents of 104 non-flooded households in the same postal district were recruited by random selection of addresses from a post flooding survey and a commercial database respectively. Having been flooded was associated with earache (RR 2.2 [1.1,4.1] p = 0.02), and a significant increase in risk of gastroenteritis with depth of flooding (RR 1.7 [0.9,3.0] p = 0.09, p for trend by flood depth = 0.04). Adults had a four-times higher risk of psychological distress defined as a score of > or = 4 in response to the 12-item General Health Questionnaire (GHQ-12) (RR 4.1 [2.6, 6.4] p < 0.0005, p for trend by flood depth = 0.01). Associations between flooding and new episodes of physical illness in adults diminished after adjustment for psychological distress. Flooding remained highly significantly associated with psychological distress after adjustment for physical illnesses. Psychological distress may explain some of the excess physical illness reported by flooded adults and possibly by children as well. Policies to promote population resilience to flooding where flood prevention has failed must include practical support for flood victims and provision of appropriate psychological support. Associations with physical illnesses affirm the need for advice and assistance with individual, household and environmental hygiene and access to medical services.