alpha-Synuclein phosphorylated at Ser129 is the main component of Lewy bodies of Parkinson's and closely related diseases. We studied, by quantitative immunoblotting, changes in the phosphorylation level of alpha-synuclein in the mouse brains subjected to cold water stress. Relative basal level of alpha-synuclein phosphorylation at Ser129 was 40% higher in the striatum compared with the hippocampus. The phosphorylation level decreased to 57% in the striatum 20 min after 5 min of cold water stress, and also in the hippocampus and cortex to lesser degrees. Recovery to basal levels took place over several hours. The stress-induced temporary dephosphorylation was of smaller magnitude in the striatum of aged (18 months) mice. These results show that alpha-synuclein phosphorylation level at Ser129 in vivo responds to physiological stimuli. Relative prominence and age sensitivity of this phenomenon in the striatum may be relevant to the pathogenesis of Parkinson's disease.