This paper inquires into the social and environmental context of a national movement in Qajar Iran that is known as the Tobacco Protest. The presentation engages with the literature on the Ottoman Empire and several other parts of the world, and reads through different classes of newly published and unpublished archival sources in order to illustrate that germs and epidemics were an important factor in the making of popular movements and revolutions in the nineteenth-century Middle East. This talk demonstrates that Iran faced a major public health crisis in 1890-92, a period that was particularly important for the formation and manifestation of the first instance of coordinated nationwide public dissent in the modern history of the country. The contention here is that in these years vast segments of Persian society, especially the poor and the underclass population, struggled perhaps more than ever before with threats and dire consequences of germs and epidemics. This was so because a considerable number of common maladies joined some new contagions to paralyze the everyday life of average people in just about all parts of the Qajar state. This widespread public health crisis added much to the suffering of the groups who had long been affected adversely by the economic and political transformations of the country over the course of the nineteenth century. Meanwhile, the response on the part of the Persian government appeared insufficient and did not fully address the main causes of the crisis. Instead, government response laid bare the characteristic inefficiency of the central administration in dealing with major forces that undermined the daily life of average people over the course of the previous years and decades. The problems that the state officials had in containing epidemics symbolized the kind of ineffectiveness that characterized their dealing with other recurrent social ills—such as poverty, food scarcity, extortion, and abuse of power by certain elements within the Qajar state—that frustrated so many different classes of the population throughout the previous years and decades. In this environment, the public health crisis became the symbolic marker of a nation in decline and many started to make new demands on the government even as the nationwide agitations related to the Tobacco Protest unfolded. In brief, then, the public health crisis of 1890–92 precipitated or provided additional justification for the agitations of the Tobacco Protest.