To identify genes whose expression changes as a function of aging, we screened mouse cDNA libraries with cDNAs from mice of different ages. Specifically, whole-mouse cDNA libraries were constructed in lambda gt10 using poly(A) RNA from young (3 month) and old (27 month) C57BL/6J inbred mice and these lambda plaques were hybridized with radioactive cDNAs made from pooled poly(A) RNA from animals 3 or 33 months of age. Five clones were isolated that showed an aging-related pattern of expression and four of these were identified by computerized sequence matching to the GenBank database: MUP2 (a major urinary protein); Q10 of the MHC locus; a cytoskeletal actin gene; and creatine kinase. One gene whose expression increases with aging and is most abundant in spleen remains unidentified. All five cDNAs showed 4-fold to 17-fold changes with aging in their steady-state mRNA levels in at least one tissue.