The selective vulnerability of limb and bulbar motor neurons is a hallmark of degenerative human motor neuron diseases such as amyotrophic lateral sclerosis (ALS). Currently, there are no known molecular characteristics to distinguish between motor neuron pools which are highly susceptible to degeneration in ALS and those populations which are resistant. Using in situ hybridization on adult rat tissue, we demonstrated that ALS-resistant motor pools robustly express mRNA for the calcium binding protein parvalbumin, while no measurable parvalbumin expression is found in ALS-sensitive motor neuron populations. In contrast, mRNA expression for each of several other calcium binding proteins such as calbindin-D28K, calretinin and calmodulin appears similar in the various motor pools. Thus, parvalbumin represents a biochemical marker of ALS-resistant motor neurons, and may provide insight into the mechanisms of resistance of certain motor neurons to disease.