The roles of personality traits, as assessed by Eysenck Personality Inventory, and of the clock gene PERIODS (PER3) were analysed on the subjective effects of prolonged wakefulness. A sample of 70 healthy participants (7 men, 63 women; M age = 24.2 yr., SD = 3.2) was studied during forced wakefulness between 7:30 p.m. and 9:30 a.m. According to Eysenck's arousal model, it was hypothesized that prolonged wakefulness might affect in a different way those classified as Introverted and Extraverted. During the forced wakefulness period, the Introverted group showed greater decrease in subjective measures of vigilance than did the Extraverted group, but no differences were observed between groups with high and low scores on Psychoticism and Neuroticism. Prolonged wakefulness had a negative effect on subjective sleepiness and mood in all three PER3 polymorphisms analysed.