Biological insults that produce profound mental retardation (MR) in humans have generally been found to produce little cognitive dysfunction in animal models. Based on the fact that impaired transfer of learning is one of the hallmark characteristics of mentally retarded humans, we proposed that this discrepancy may largely reflect the common use of a single learning task as the critical cognitive index rather than an assessment of cumulative learning. Consistent with this hypothesis, rats exposed to prenatal hyperphenylalaninemia (a model of maternal PKU) evidenced significant impairment when tested on a series of 10 problems designed to allow for positive transfer of learning. This same treatment, however, did not alter learning rate of the individual tasks that comprised this series when presented singly to experimentally naive animals. Deficient transfer of learning contributed significantly to the impairment observed in the maternal PKU group. These results support the hypothesis that the assessment of cumulative learning is an important component of animal models of impaired cognitive development.