An asthma-like condition has been reported among aluminum smelter potroom workers. The pathophysiologic mechanisms and the causative agent involved are unknown. Inasmuch as gene polymorphisms are associated with asthma in the general population, the authors of this case-control study examined whether polymorphisms were associated with the development of potroom asthma. Genotyping was performed for the beta2-adrenoreceptor, high-affinity Ig (immunoglobulin) E receptor, and Tumor Necrosis Factor on potroom workers who developed a new asthma-like condition and on individuals who did not develop respiratory problems. No associations were found between potroom asthma case status and genotype. The asthma-like condition associated with potroom work remains poorly understood. Future investigations of genetic susceptibility and occupational asthma may provide pathophysiologic insights into these work-related conditions, but larger numbers of subjects will be required.