In this questionnaire study, the authors compared the prevalence of certain symptoms and signs associated with Sick Building Syndrome and perceptions relative to environmental discomfort of employees in a central-air-conditioned dropping center and in natural-ventilation commercial shops located on the streets of Niteroi, Rio de Janeiro, Brazil. There was a statistically significant higher prevalence of symptoms (e.g., water and itching of eyes, sore throat, nose irritation, difficulty breathing, skin irritation, sneezing) that were characteristic of Sick Building Syndrome in the air-conditioned building than in the naturally ventilated stores. The results indicated that there exists a continuing need for further research in Brazilian work environments.