We developed two highly sensitive enzyme immunoassays for beta-protein with different specificities. One is specific for beta 1-40, while the other is equally sensitive to beta 1-38, beta 1-39, beta 1-40, and beta 1-42. With the enzyme immunoassays we investigated whether the soluble fraction from brain tissue contains beta 1-40 or other species of beta-protein. Aged control and Alzheimer's diseased brains showed highly variable values of beta 1-40, which was found to be the major beta species in their extracts. High tissue content of soluble beta 1-40 was not correlated to the abundance of senile plaques but was invariably associated with cerebral amyloid angiopathy. Thus, the tissue level of soluble beta 1-40 should be useful for the quantification of cerebral amyloid angiopathy.