1. Fyn, a member of Src-family tyrosine kinases, is implicated in both brain development and adult brain function. Recent studies have identified some Fyn substrates, however, little is known about the transcriptional targets for Fyn mediated signaling pathways. In the present study, we sought to identify targets downstream of Fyn in vivo. 2. We compared genes expressed in adult hippocampi of wild-type and fyn-deficient mice using gene chips containing more than 12,000 genes. 3. The results showed that 559 transcripts were expressed differentially between these mice. Expression of 20 genes including a substantial number of myelin-associated genes was strongly repressed in fyn-deficient mice. 4. Reduced expression of these myelin-associated genes, such as MBP and MOG, in fyn-deficient mice was also confirmed by real-time PCR and northern blotting, arguing that Fyn is important for function and development of oligodendrocytes. 5. Further analysis of the genes that are differently expressed in fyn-deficient mice may shed light on the molecular mechanism by which Fyn regulates adult neural function.