Young people are of particular importance in state policies against AIDS. The present study investigated the attitude toward HIV/AIDS and related socio-cultural factors among 600 high school students in Shiraz, Iran. The method of sampling is a stratified one and the instrument for collecting data is a self-administrated questionnaire. In this research, attitude has three dimensions-knowledge, emotion and tendency to action. Descriptive statistics showed that students did not have enough knowledge about HIV/AIDS. The 44.3% of students had low knowledge, 36.9% moderate knowledge and only 18.8% had high knowledge. Also the results indicated that attitude for 69.8% of student has in middle level, 15.4% positive and 14.9% negative. Moreover, results suggested that loyalty to Islamic religious beliefs have an important role on attitude toward this disease. Major of study, sex, mothers occupation and use of some mass media such as books and newspapers were other main influencing factors in the students attitude. Furthermore, this study showed that parent education, major of study, fathers occupation and use of books and the internet are the most important variables affecting on the participants knowledge. Age, sex, parents education, religious beliefs, use of some mass media such as TV, the internet, newspapers, satellite and books affect emotion. Finally, there is a relationship between religious beliefs, sex and major of study, use of satellite, television, radio and books with tendency to action.