A cross-sectional study measured the frequency of self-reported stress symptoms among a weighted random sample of medical students in Isfahan, Islamic Republic of Iran. The data were gathered using the Kessler 10-item psychological distress scale. The overall prevalence of stress among 222 students was 61.3% and there were no statistically significant differences in stress levels between students in the pre-clinical and clinical phases or different years of study. Married students had significantly lower scores than single students but there were no differences between the sexes. Students who chose to study medicine had lower stress scores than those who were influenced by family or had no choice about the subject. Students with mild to moderate stress were significantly more likely to suffer physical problems (OR = 4.42). Interventions are needed to tackle stress and improve Iranian medical students' physical and psychological well-being.