This study examined the separate and interactive effects of caffeine, sleep restriction, and task-induced laboratory stress in 96 healthy male and female volunteers. Participants alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Finapres measurements of blood pressure, cardiac output, and total peripheral resistance showed that caffeine produced persistent blood pressure increases with a vascular hemodynamic profile. Sleep restriction produced a pronounced vascular response not associated with appreciable changes in blood pressure, whereas blood pressure increases induced by cognitive activity showed mixed cardiac and vascular responses. The findings suggest that life-long dietary caffeine may contribute significantly to the development of cardiovascular disease.