Systematic investigation on the effects of human exposure to environmental pollution using scientific methodology only began in the 20th century as a consequence of several environmental accidents followed by an unexpected mortality increase above expected mortality and as a result of observational epidemiological and toxicological studies conducted on animals in developed countries. This article reports the experience of the Experimental Air Pollution Laboratory at the School of Medicine, University of São Paulo, concerning the respiratory system and pathophysiological mechanisms involved in responses to exposure to pollution using toxicological and experimental procedures, complemented by observational epidemiological studies conducted in the city of São Paulo. It also describes these epidemiological studies, pointing out that air pollution is harmful to public health, not only among susceptible groups but also in the general population, even when the concentration of pollutants is below the limits set by environmental legislation. The study provides valuable information to support the political and economic decision-making processes aimed at preserving the environment and enhancing quality of life.