With the advent of recombinant DNA technology the mouse has become a favored model organism in brain research. Numerous mouse strains are available to use as a host for carrying genetic alteration induced by targeted or random mutagenesis. Most strains differ in their genetic makeup and phenotypical characteristics. The choice of the host strain thus can be crucial for the analysis of functional effects of the induced mutation. In the present paper we analyze the behavior of two related outbred albino strains of mice, ICR and CD1, that are often used in transgenic research. Using two frequently employed learning tasks, the Morris water maze (MWM) and the context-dependent fear conditioning (CFC) as well as other behavioral tests, we demonstrate significant performance differences between the strains. ICR suffers from a severe visual impairment making this strain difficult to use in several behavioral paradigms that require good visual perception, e.g. the MWM. CD1 does not suffer from grossly impaired vision but, similarly to the ICR strain, CD1 mice exhibit decreased freezing in all phases of CFC. Although the strains are able to learn, such deficits can render them significantly impaired dependent on the performance demands of the cognitive test employed. Our findings underscore the need for careful examination of the characteristics of the host strain, the choice of which must be made in accordance with the expected functional alterations induced by the mutation.