A.I.D.S as a worldwide crisis continues to spread in Iran too. The number of afflicted patients has reached 5780 subjects; most of them are between 20 to 40 years of age. Prevention is one of the most effective methods to combat this human hazard. Promotion of general knowledge is thought to be the preliminary measure in this regard. Although, schools have turned to be the most favorable environment' for health education, the issue of the group to afford training has remained controversial in our country yet. The aim of this research is a comparison between the effect of training performed by teachers or health staff on the knowledge of students of the first high school grade in Bushehr Iran. A total of 684 male and female students of the first high school grade were selected according to cluster random sampling. The selected students were divided into two groups and training for A.I.D.S using the same contents was done by their teachers and health staff separately. Before intervention, the mean knowledge scores of female & male students about A.I.D.S were 16.68 and 15.52, respectively. There was no significant difference in female students in two groups but teacher trained male students showed an increment score of 4.17 while in health staff ones, the score increment was 2.22 (P<0.01). In conclusion, the level of knowledge about A.I.D.S was not satisfactory in the high school students in Bushehr and for education in this group; their sex in conjunction to different training methods should be considered.