Susceptibility to stress would presumably be different from person to person and be affected by the cause of the given stress. The purpose of this study was to investigate the interactive effects of task difficulty and subject's personality on mood and autonomic nervous function when stress was induced experimentally by tasks involving 3 degrees of difficulty: easy (Task A), difficult but controllable (Task B), and very difficult and uncontrollable (Task C). Twelve healthy female subjects volunteered for the experiment. We assessed their personalities using the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire. Mood states were evaluated by a profile of mood states and a frontal alpha laterality ratio (FALR). Autonomic nervous function was estimated by a spectral analysis of heart rate variability (HRV). Repeated measures analysis of variance applied to two groups (low- and high-) divided by a median split of MMPI clinical scales, revealed significant interactions of time course × task difficulty × Hs (hypochondriasis) in FALR and time course × task difficulty × Pt (psychasthenia) in a low-frequency component and in a high-frequency component of HRV, and in FALR. The differences between low- and high-Hs, and low- and high-Pt were more obvious in Task B session. High-Hs group, whose members tend to place overemphasis on existing physical disorders, showed more negative FALR throughout the session, which would indicate prolonged negative mood possibly due to the task. High-Pt group, whose members tend to be susceptible to stress, showed sympathetic predominance during task period and parasympathetic predominance after task period, which would imply a tendency to overreact. These results suggest that task difficulties would affect mood states assessed by FALR and/or autonomic nervous function differently depending on the subject's personality, especially on Hs and Pt.