This study was designed to examine the associations of an exaggerated systolic blood pressure (SBP) response to exercise with the indices of nitric oxide (NO) bioavailability, oxidative stress, inflammation and arterial stiffness in normotensive females. The subjects included 84 normotensive females without a history of cardiovascular disease or stroke who were not taking any medications. Each subject performed a multistage graded submaximal exercise stress test using an electric bicycle ergometer, and their blood pressure was measured at rest and during the last minute of each stage. The brachial-ankle pulse wave velocity, plasma nitrate/nitrite (NO), plasma thiobarbituric acid-reactive substances, high-sensitivity C-reactive protein (hs-CRP) and fibrinogen levels and the white blood cell count were measured. An exaggerated SBP response to exercise was defined according to the criteria of the Framingham Study (peak SBP: ⩾190 mm Hg). An exaggerated SBP response to exercise was observed in 27 subjects. A multiple logistic regression analysis revealed that the hs-CRP (odds ratio (OR): 1.05, 95% confidence interval (CI): 1.03-1.07, P=0.015) and plasma NO levels (OR: 0.92, 95% CI: 0.87-0.98, P=0.014) were significantly associated with an exaggerated SBP response to exercise. Furthermore, the percent change in SBP was found to be significantly associated with an increase in the hs-CRP (P for trend=0.006) and a decrease in the plasma NO levels (P for trend=0.001). These results suggest that an exaggerated SBP response to exercise was associated with the NO bioavailability and inflammatory status in normotensive females.