Drinking coffee results in an increase in blood pressure (BP) after an interval of caffeine abstinence. During chronic caffeine intake this pressor response disappears and adaptation to the circulatory effects of caffeine develops. This study was designed to determine whether a pressor response to coffee occurs during chronic caffeine intake if low basal plasma caffeine levels are achieved by a period of caffeine abstinence, defined by individual plasma caffeine half-life. In 8 normotensive subjects, circulatory measurements were studied after ingestion of coffee in 2 strengths, decaffeinated coffee and hot water after a caffeine abstinence of 4.5 times individual caffeine half-life. These measurements were compared to the same protocol without intervention. Coffee of both strengths resulted in a similar increase in BP (diastolic BP +/- 15%). The coffee-induced increase in forearm blood flow and plasma epinephrine levels were less pronounced. Decaffeinated coffee induced a smaller increase of diastolic BP, and after water, no changes were observed. Additionally, a negative correlation was found between the coffee-induced BP increase and basal plasma caffeine level in a group of 30 normotensive subjects (r = -0.71, p less than 0.001). During chronic caffeine intake, subjects with short plasma caffeine half-life are exposed to a pressor response after drinking coffee, despite the phenomenon of adaptation.