Induction of the proto-oncogene c-fos has been associated with a number of neural and behavioral responses to acute stimuli. Behavioral characterization of mice containing a mutant c-fos allele created via homologous recombination-based gene targeting was performed to analyze the role of this protein in baseline neurological properties as well as paradigms that require neural adaptive responses. Performance of 9 out of 11 c-fos-deficient animals was impaired in the spatial version of the Morris water task. However, this poor performance in the spatial version of the task was highly correlated to their performance in the non-spatial version of the task which suggests that they have a behavioral impairment that interrupts their ability to perform adequately on both versions of the task with the same proficiency as wild-type and heterozygous litter mates. To examine learning impairments further, a simple left/right discrimination in a T-maze was used. Mutants were not impaired in this simple learning task. These results suggest that c-fos mutants have some behavioral impairments that interfere with evaluation of complex learning on the Morris water task, but because all genotypes could perform a simple discrimination task, it is clear that c-fos is not essential for this simpler form of learning and memory.