Differences between Alzheimer and control fibroblast [Ca2+ + Mg2+]-dependent ATPase activity at free Ca2+ concentration considerably higher than physiologic concentrations were observed. At 50 microM free Ca2+, Alzheimer and control fibroblast homogenates exhibited maximum velocity values ranging from 8 to 25 nmoles phosphate released/min/mg protein. Higher free Ca2+ (350 microM) inhibited control fibroblast ATPase activity approximately 77%; whereas, Alzheimer fibroblasts retained greater than 75% starting activity. Although the pathophysiological significance of these findings is at present unclear, these data suggest the Ca2+ pump of Alzheimer fibroblasts behaves differently in the presence of high free Ca2+. Such behavior may be of potential diagnostic value.