The free radical neuromodulator, nitric oxide (NO) has been implicated as a neurotoxin. Neurons containing NO synthase (NOS) also contain NADPH-diaphorase (NADPH-d) and are resistant to NO toxicity. We report that NADPH-d-containing neurons within the striatum are spared in patients with Parkinson's (PD) and Alzheimer's disease (AD). However, a number of these neurons in both diseases appeared shrunken or bulbous with foreshortened dendritic processes. Quantitative analysis of cell areas revealed a significant difference only in the size of putamenal AD neurons which were decreased compared to normal controls. The possible involvement of NO in the neuropathogenesis of striatal derangement is discussed.