ErbB4 is an important brain receptor for the neuregulin1 growth factor. A conditional knock-out mouse was developed lacking both alleles of the erbB4 gene in neurons/glia, and one allele in other cells. The conditional mutant mice were compared to heterozygous null (one null allele and one wildtype allele in all tissues) and wildtype control (no gene deletion) littermates in a battery of behavioral tests. Conditional mutants displayed a lower level of spontaneous motor activity and reduced grip strength compared to wildtype control mice. Group mean scores of heterozygous nulls were intermediate on these measures. However, heterozygous nulls were delayed in motor development and male heterozygous nulls demonstrated altered cue use in a Morris maze learning and memory task relative to both wildtype control and conditional mutant mice. These findings were interpreted based on more detailed analysis of the behavioral data and considerations of the complex nature and multiple roles of the neuregulin/erbB4 system in the nervous system.