Reverse phase HPLC analysis of somatostatin immunoreactivity in the cerebral cortex in elderly normal individuals revealed that the majority of the immunoreactivity co-eluted with synthetic somatostatin-14. While an immunoreactive peak corresponding to somatostatin-28 was not detected there was a peak of immunoreactivity which eluted after somatostatin-14. In cases of senile dementia of Alzheimer type (SDAT), where abundant neurofibrillary tangles and senile plaques (density greater than 30 per 1.3-mm2 field) were present in the cerebral cortex, somatostatin immunoreactivity was found to be significantly decreased in either the frontal or temporal cortex. Chromatographic analysis, however, revealed that both the major immunoreactive peaks detected in the normal group were reduced in SDAT in the temporal and frontal cortex. Using a punch microdissection technique somatostatin immunoreactivity has been assessed in the nucleus of Meynert and amygdala of SDAT and elderly normal cases. While there was no change in somatostatin immunoreactivity in the nucleus of Meynert in the SDAT group, tissue punches taken from the amygdala revealed a selective decrease in somatostatin immunoreactivity in the basal nucleus, in the SDAT cases.