Animal and human studies show that polyunsaturated fatty acids (P) are oxidized more rapidly than saturated fatty acids (S). There are indications that diets high in P/S ratio result in a relatively high resting metabolic rate (RMR) and high diet induced thermogenesis (DIT). However, studies with human subjects are limited. The effect of dietary fatty acid composition on energy metabolism was studied in 6 male subjects, age 25-48 y. Two diets were supplied, each over a period of 14 days, in a randomized crossover design with a washout period of 14 days. P/S ratios of the diets were 0.19 and 1.67. On day 14, RMR was determined in the morning in fasting state by means of indirect calorimetry (ventilated hood), followed by a 4 hour measurement of the DIT after consumption of a standardized meal of 3.3 MJ with the same fatty acid composition as during the dietary period. The meal contained 46, 37, and 17 % energy as fat, carbohydrate, and protein, respectively. RMR after the period with the high P/S diet was significantly higher than after the period of the low P/S diet. The average difference (+/- SD) was 0.17 +/- 0.14 kJ/min or 3.6 +/- 2.7 % of RMR. The DIT was also higher in all subjects during a breakfast with a high P/S ratio. The average difference was 0.29 +/- 0.16 kJ/min, which is 22.1 +/- 12.6 % of DIT. The study showed that a prolonged food intake of a diet with a high P/S ratio results in a relatively high RMR and DIT. These results indicate the importance of dietary lipid profile in the treatment of obesity.