Introduction: Acquired immunodeficiency syndrome (AIDS) is one of the most serious health problems and one of the deadliest communicable infectious diseases of this century. Increasing knowledge and changing wrong beliefs and behaviors is the best way to prevent this disease. The purpose of this study was to determine the knowledge and attitude of high school students about AIDS. Material and methods: This descriptive-analytical study was performed on 500 high school students at secondary high school level in experimental field in Rasht City. At first, some schools were randomly selected as clusters and then, the required samples from each school were selected by systematic random sampling. The research tool used in this study was a questionnaire consisting of three sections: general information, knowledge assessment, and attitude assessment. The data were entered into SPSS software and analyzed using chi(2) test. Results: In terms of knowledge level, 347 (69.4%) students had sufficient knowledge, 142 (28.4%) presented medium, and 11 (2.2%) insufficient level of AIDS knowledge. In terms of attitude level, 354 (70.8%) had positive attitude, 145 (29%) had neutral attitude, and 1 (0.2%) had negative attitude. There was a statistically significant difference between the level of knowledge of students with gender, educational grade, and school type (p = 0.0001). Conclusions: The results of this study indicate the necessity of continuation of formal and informal education, and efforts of educational, health, and cultural officials in order to teach AIDS control and prevention methods.