We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (-4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29 and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the left superior partietal cortex and on the left prefrontal cortex simultaneous increases in [HbO2] as well as [HbT] in both cortical regions in the healthy elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2] and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.