A distinctive form of ulcerative panniculitis develops in a subset of persons with alpha-1-antitrypsin deficiency. This association may be more widely recognized if routine determinations of alpha-1-antitrypsin are performed on patients in whom neutrophilic, ulcerative panniculitis develops without specific, defined underlying causes. Therapies that appear to be of the greatest potential benefit include treatment with dapsone and alpha-1-proteinase inhibitor replacement. Astute recognition of alpha-1-antitrypsin-deficient panniculitis and assessment of response to these and other therapies will ultimately lead to a more complete understanding of the cause of this distinctive and uniquely associated disease.