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Seropositive rheumatoid arthritis (RA) has been considered to be a stochastic process; 1 however, careful consideration of the natural history of RA and examination of some of the known environmental risk factors would suggest otherwise. Rather than a set of random initiating events, it is hypothesized here that there is an overarching etiological trigger factor to account for some of the known risk factors for disease development. The lung has been considered to be the initiating site of seropositive RA as a result of local rheumatoid factor and anti-citrullinated peptide (anti-CCP) antibody generation. 2 In this paper, it is hypothesized that inhalation of cadmium is an important etiological factor in seropositive RA development.