Over two years, the Vaccine Adverse Event Reporting System reported that 0.042% of all anthrax vaccine (Biothrax, Bioport Corporation) doses administered were associated with cutaneous reactions, half of which were eczematous. This case series attempts to immunologically detail this eczematous reaction in four patients by measuring anthrax vaccine-specific cell mediated immunity (ASCMI), profiling TH1 and TH2 cytokine response to the anthrax vaccine in vitro, and analyzing of skin biopsy specimens. Results demonstrated that (1) ASCMI was variable and likely unrelated to this reaction; (2) a lack of TH1 cytokine response to anthrax vaccine may be associated with an increased risk of this eczematous reaction; and (3) skin biopsy findings were nonspecific but supportive of a clinical diagnosis of eczema. Future studies with more patients may yield data to further characterize the ASCMI response and cytokine profiles among patients with this type of reaction.