An increasing number of environmental agents are being investigated as possible risk factors in the etiology of certain connective tissue disorders. Exposure to a variety of therapeutic agents, foods and dietary supplements, occupational and other toxic exposures, and infectious agents has been associated with the onset of lupus-like disorders. The mechanisms by which these agents might induce lupus remain unknown but may involve alteration of cellular components or activation of the immune system. Individual host susceptibility factors, including pre-existing organ dysfunction and particular metabolic enzyme or immunogenetic phenotypes, may also be important risk factors for development of environmentally-associated lupus-like disorders. Awareness of the many environmental agents implicated with lupus and related disorders, and dissection of their pathogenetic mechanisms through appropriate case-controlled investigations, may identify additional toxic agents and may lead to a better understanding of the idiopathic lupus syndromes.