Progesterone has neuroprotective effects including augmentation of myelination in the central and peripheral nervous system. This study was designed to determine if demyelinating lesions in the cerebellum resulting from canine distemper virus (CDV) infection are associated with progesterone levels. Progesterone was measured using radioinummoassay in samples of the cerebellum, corpus callosum, medulla oblongata, parietal, frontal, temporal, and occipital cortices as well as cerebrospinal fluid (CSF) and plasma collected from ten CDV infected and six non-infected dogs. The cerebellum progesterone level was significantly different between CDV infected (0.66 +/- 0.09 ng/g) and control dogs (1.14 +/- 0.09 ng/g) (p < 0.001); however, no difference was observed for the other CNS regions, plasma and CSF (p > 0.05). The cerebellum progesterone level was also significantly different between acute (0.71 +/- 0.05 ng/g) and chronic cases (0.61 +/- 0.09 ng/g) (p < 0.05). The CDV infected cerebella were also categorized histopathologically according to the severity of demyelinating lesions as mild (n = 5), moderate (n = 2), or severe (n = 3) among which the cerebellum progesterone level was significantly different (p < 0.05). Progesterone concentration was 0.71 +/- 0.05 ng/g in mild, 0.65 +/- 0.10 ng/g in moderate, and 0.56 +/- 0.07 ng/g in severe cases.