A large body of evidence has accumulated that disturbed cellular homeostasis of calcium ions might play a pivotal role in the pathophysiology of Alzheimer's disease (AD). Besides important implications of calcium as second messenger it was discussed that sustained elevation in cytosolic free calcium concentration ([Ca 2 + ] i ) might be a prerequisite to the intranucleosomal DNA cleavage and programmed cell death. Calcium mediated processes during age or neurodegeneration are apparently not restricted to cells of the nervous system, but may also be investigated in peripheral cells as skin fibroblasts or lymphocytes. However, data are not homogenous, since [Ca 2 + ] i was found to be increased, decreased or unchanged (Peterson et al., 1992). Recent findings indicate, that other mechanisms, involved in calcium homeostasis, might contribute to AD. Thus, using skin fibroblasts it was found that dysfunction of K+-channels might be one of these factors (Etcheberrygary at al., 1993).With respect to the importance of this finding we have investigated if similar alterations could be found in lymphocytes. Basal values of [Ca 2 + ] i , the PHA (25 [mu ]g/ml) induced increase as well as the influence of the K+-channel inhibitor TEA were investigated in lymphocytes of 43 persons. Twenty of them (9 females, 11 males; age from 39 to 83 years) were diagnosed as [ldquo ]probable[rdquo ] AD according to the NINCDS-ADRDA and DSM-III-R criteria. Twenty three healthy persons (9 females, 14 males; age from 37 to 89 years) served as non-affected control group. [Ca 2 + ] i was investigated using a fluorescence spectrophotometer (Perkin Elmer LS 50) as previously described (Bondy et al., 1994). The influence of the K+-channel blocker tetraethylammonium (TEA) was evaluated by preincubating the cells for 2 min with 100 mM TEA before the [Ca 2 + ] i measurements.The results being summarized in table 1, demonstrate that basal and PHA stimulated [Ca 2 + ] i values are slightly but significantly increased in AD patients. In contrast to that, the net [Ca 2 + ] i increase after stimulation with the mitogen PHA was not altered in AD patients as compared to healthy controls. Preincubating the cells with the K+-channel blocker TEA led to a 44% inhibition of the PHA-induced [Ca 2 + ] i increase in healthy controls. This inhibition was significantly and much less pronounced in lymphocytes of AD patients (23%). The individual data even show, that there was almost no overlap between the groups, since only 3 AD patients inhibited more than 30%, but only 1 control less than 30%.Our results demonstrate, that besides having important pathophysiological implications, measurement of [Ca 2 + ] i and of the influence of several agents on calcium homeostasis in peripheral cells might even be of diagnostic significance.