We obtained serum samples and measured alpha 1-antichymotrypsin (ACT) levels in 36 pairs of consecutive probable Alzheimer's disease (AD) patients and age- and sex-matched, cognitively intact control subjects. Serum ACT was measured by radial immunodiffusion. Unique to this study, we found that ACT levels rose significantly with age within controls (but not within AD cases), thus ACT may be related to the aging process. Consistent with other reports, we found that AD cases had greater serum ACT in 27 of 36 pairs [mean difference = 135.5 (SE = 50.8) mg/l (p < 0.05)]. Severity and duration of AD were not significantly associated with the observed difference. The ACT increase observed in AD is not sufficient to recommend ACT's use as a diagnostic marker for AD. Because adult Down's syndrome (DS) persons are known to have pathologic features of AD, we also measured serum ACT levels in 11 adult, noninstitutionalized, DS persons paired with 11 age- and sex-matched, volunteer control subjects; we found no statistically significant difference. The unexpected age-associated increase in ACT among normal controls could be an indicator of early amyloid plaque formation. Future studies comparing ACT levels in both serum and cerebrospinal fluid should help to clarify the origin of ACT found in amyloid plaques and its value as a diagnostic marker for AD.