This study was undertaken to determine whether prenatal exposure to influenza epidemics increases the risk of mental handicap. The monthly birth frequencies of 827 first-admission individuals (mean age at admission 13 years) with a primary diagnosis of non-specific mental retardation, discharged from psychiatric hospitals in England and Wales, were examined in relation to the monthly death rates from influenza over the period 1953-1980. The relative risk of developing mental handicap when exposed to influenza epidemics during mid-gestation was assessed by a generalized linear model. Increased death rates from influenza, a measure of prevalence of the infection, were significantly associated with an increase in births of mentally handicapped individuals 6 months later. For every 1000 female deaths from influenza there was a 17% increase in births of mentally handicapped individuals 6 months later. Maternal exposure to influenza at approximately the third to fourth month of gestation may be risk factor for developing mental handicap.