The possible combined effects of caffeine and exercise on blood pressure (BP) regulation were examined in 34 healthy, normotensive (BP less than 135/85 mm Hg) young men (mean age 27 +/- 3 years) in a placebo-controlled, double-blind crossover design. Each subject performed submaximal and symptom-limited maximal supine bicycle exercise 1 hour apart after ingestion of placebo or caffeine (3.3 mg/kg). Heart rate, BP, cardiac output and peripheral vascular resistance were compared for placebo and caffeine days. Postdrug baseline showed that caffeine increased systolic and diastolic BP and peripheral vascular resistance (p less than 0.001 for each) and decreased heart rate (p less than 0.01) but did not change stroke volume or cardiac output. BP and vascular resistance effects of caffeine remained during submaximal exercise resulting in an additive increase in BP while negative chronotropic effects of caffeine disappeared. At maximal exercise substantially more subjects (15 on caffeine vs 7 on placebo, p less than 0.02) had systolic BP greater than or equal to 230 mm Hg and/or greater than or equal to 100 mm Hg for diastolic BP. Plasma norepinephrine levels were not significantly different across days, but epinephrine was higher at maximal exercise and cortisol was increased post-drug and throughout maximal exercise on caffeine days. Data indicate that caffeine increases BP additively during submaximal exercise and may cause excessive BP responses at maximal exercise for some individuals. The pressor effects of caffeine appear to be due to increasing vascular resistance rather than cardiac output.