The cerebral cortical sphingomyelinase (SMase) activities were detected in the cytosolic and the membrane fractions of cerebral cortex, hippocampus, cerebellum, brainstem, and thalamus/midbrain of senescence-accelerated mouse-prone/10 (SAM-P/10) and SAM-resistant/1 (SAM-R/1) with advancing age, respectively. The SMase activity was increased uniquely in the membrane fraction of the cerebral cortex of SAM-P/10 in an age-dependent manner; The enzyme activities of 10 and 17 months of age were about 25 and 30% higher than those of 2 months of age, respectively. This observation implicates that the membrane-associated SMase activity might be related with accelerated senescence. The cerebral cortical SMase was eluted in a molecular mass of approximately 400 kDa on a gel filtration chromatography and was active in a broad range of pH from 4 to 9. It was also suggested that phosphorylation may be one of the mechanisms regulating the enzyme activity, but not responsible for the increased activity with advancing age.