The largest and most extensive documented dengue epidemic in Puerto Rico struck an estimated 355,000 Puerto Rican residents from July–December 1977. The mixed epidemic of dengue types 2 and 3 coincided with a Caribbean pandemic of dengue type 1, first introduced into the western hemisphere in early 1977 and into Puerto Rico in the fall of that year. Health officials assembled a team to assess the epidemic and mounted a campaign to end it. Attempts to monitor the incidence and spread of dengue were confounded by simultaneous co-circulation of influenza virus, underscoring problems in formulating public health strategies dependent on nonspecific clinical and epidemiologic case criteria, and the need for rapid and reliable diagnostic capabilities. Despite co-circulation of multiple dengue serotypes, a risk factor associated with severe and fatal dengue hemorrhagic fever (DHF) in Southeast Asia, hospital and death certificate surveillance disclosed no cases of DHF in Puerto Rico. The epidemic serves as a reminder that when preventive measures are impossible or infeasible, developed countries with high living standards may be susceptible to large scale epidemics of infectious diseases.