The objective of the study was to investigate the unique and interactive effects of the controllability of a task and mental effort required by that task on cardiovascular and endocrine reactivity, when both were manipulated independently. A 2 x 2 factorial design was used, with two levels of mental effort and two levels of control. Twenty-four healthy male subjects participated in each experimental condition. Heart rate, blood pressure, catecholamine and cortisol responses were determined. High effort lead to greater increases in heart rate, blood pressure and norepinephrine levels. Uncontrollability lead to higher cortisol, blood pressure and norepinephrine responses. In addition, there was an effort x control interaction effect on the diastolic blood pressure response. In conclusion, effort has clear sympathetic effects, whereas control influences both the sympathetic nervous system and the release of cortisol. Having control seems to be most beneficial in high effort situations, at least with respect to sympathetic reactivity.