This article describes three periods in Brazil's modern history when governmental action was (or was not) taken against smallpox: first, when smallpox control became a priority in the Brazilian sanitary agenda from the nineteenth century to the beginning of the twentieth century; second, when it was rendered politically invisible during decades when greater attention was given to yellow fever and malaria control; third, when it reappeared at the centre of Brazilian health policy in the 1960s until its eventual eradication in 1973. Smallpox control in the latter two periods is suffused with paradox. For example, evidence suggests that the nearly fifty-year absence or lack of policies and agencies to deal with smallpox actually favoured the mobilization of local, national and international resources once the eradication programme was launched in 1966; these new approaches were accelerated from 1969 until the completion of eradication in 1973. Equally paradoxical, it was during the specific context of the military regime after 1964 that the Brazilian health system developed the capacity to mobilize existing but dispersed resources and flexibly to innovate, incorporate, and adapt new policies. Another important element in this period was institutional learning based on other vertical programmes such as the malaria eradication campaign. Although the Brazilian smallpox eradication programme was constrained by international agencies and by bilateral co-operation with the United States, the period after 1964 offered opportunities for the realization of a new and wide-ranging national health capacity including the creation of a national system of epidemiological surveillance and a national childhood immunization programme. It also saw the empowerment of young physicians who would later come to occupy key positions in Brazilian public health and in international health organizations.