An increase in the polyunsaturated to saturated fatty acid ratio (P:S) in the diet has been reported to reduce blood pressure in man. We have investigated whether an increase in the percentage of saturated fatty acids in the typical Mediterranean diet would affect blood pressure in a sample of healthy rural population of southern Italy. Fifty-seven non-hospitalized normotensive volunteers (29 male, 28 female, aged 30-50 years) were studied. After a 2-week baseline period on their customary diet (P:S = 0.44), they underwent a 6-week isocaloric dietary intervention with a 70% increase in energy from saturated fatty acids and a corresponding decrease in carbohydrate and mono-unsaturated fat (P:S = 0.23). Thereafter they returned to their usual diet and were followed-up for 6 more weeks (switch-back period). By the end of the intervention period, systolic pressure was increased by 2.6 mmHg in men (P less than 0.05) and by 4.8 mmHg in women (P less than 0.01). Diastolic pressure was not significantly increased, although a significant linear regression of the group average blood pressure over time was observed for both systolic (0.161 mmHg, P less than 0.01) and diastolic pressure (0.107 mmHg, P less than 0.01). After returning to their customary diet, blood pressure returned to baseline (-0.212 mmHg, P less than 0.05 systolic and -0.226 mmHg, P less than 0.01 diastolic). No significant change in body weight occurred throughout the study. These findings suggest that changes in the saturated fatty acid content of the diet with moderate change in the dietary P:S ratio can influence blood pressure to a significant extent.