BACKGROUND: Natural products are proved to play a good role as an alternative to synthetic chemicals in many clinical conditions. Hypercholesterolemia is the most important risk factor for atherosclerosis. Previous studies showed that nigella sativa L. has both antioxidant and lipid lowering potentials. THE AIM OF THIS STUDY: To evaluate the efficacy of the seeds of nigella sativa on the treatment of hyperlipidemia. METHODS: In this randomized, placebo controlled clinical trial which was conducted in Isfahan city (Iran), 88 subjects aged > or =18 years with a total cholesterol concentration >200 mg/dl were included. According to the patients" profiles number, they were randomized to receive either N. sativa capsules or the matching placebo. Each N sativa capsule contained 500 +/- 10 mg N. sativa crushed seeds, and patients had to take 2 g N. sativa per day for 4 weeks. Fasting baseline laboratory values (fasting blood sugar, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride) were obtained for all parameters on each subject prior to the start of the study and at the end of 4 weeks. RESULTS: In our study a significant decrease was observed in the concentration of total cholesterol (4.78%), Low density lipoprotein (7.6%) and Triglyceride (16.65%), and this decrease was more significant for TG concentration. N. sativa had not any beneficial effects on fasting blood sugar and High density lipoprotein. CONCLUSION: According to the results of our present study it seems that N. sativa may have some beneficial therapeutic effects in the treatment of hyperlipidemia. However, further investigations with a larger sample size are necessary.