This was a large population-based study to develop and validate the Iranian version of the Short Form Health Survey (SF-36) for use in health related quality of life assessment in Iran. A culturally comparable questionnaire was developed and pilot tested. Then, the Iranian version of the SF-36 was administered to a random sample of 4163 healthy individuals aged 15 years and over in Tehran. The mean age of the respondents was 35.1 (SD = 16.0) years, 52% were female, mostly married (58%) and the mean years of their formal education was 10.0 (SD = 4.5). Reliability was estimated using the internal consistency and validity was assessed using known groups comparison and convergent validity. In addition factor analysis was performed. The internal consistency (to test reliability) showed that all eight SF-36 scales met the minimum reliability standard, the Cronbach's alpha coefficients ranging from 0.77 to 0.90 with the exception of the vitality scale (alpha = 0.65). Known groups comparison showed that in all scales the SF-36 discriminated between men and women, and old and the young respondents as anticipated (all p values less than 0.05). Convergent validity (to test scaling assumptions) using each item correlation with its hypothesized scale showed satisfactory results (all correlation above 0.40 ranging from 0.58 to 0.95). Factor analysis identified two principal components that jointly accounted for 65.9% of the variance. In general, the Iranian version of the SF-36 performed well and the findings suggest that it is a reliable and valid measure of health related quality of life among the general population.