Caffeine is the most widely consumed pharmacologically active substance in the world, and a key issue concerning its possible implications for human health is whether it has persistent (i.e., chronic) physiological effects on habitual consumers. This study examined blood pressure, heart rate (HR), electromyogram (EMG), and skin conductance level (SCL) in 36 healthy men and women exposed to a pattern of moderate intake. A double-blind placebo-controlled crossover design with counterbalancing was used in which all subjects participated in four experimental conditions involving the ingestion of placebo or caffeine three times daily for 6 days followed by a seventh ("challenge") day of placebo or caffeine ingestion. Results confirmed that caffeine has significant pressor effects, and these were found to be additive to the pressor action of a laboratory stressor. Following habitual consumption of the drug, pressor effects were diminished (indicative of tolerance) but not eliminated. Effects of caffeine on other parameters were either modest (HR and EMG) or negligible (SCL). Considering the near-universal use of caffeine, the persistent pressor effects observed in this study have important implications for clinical practice and public health.