Context: Evidence for an association between alcohol consumption and activity of the hypothalamic-pituitary-adrenal (HPA) axis is inconclusive.

Objective: Our objective was to assess the relationship between indices of alcohol consumption and salivary cortisol concentration.

Design: This was a cross-sectional study of alcohol consumption and cortisol secretion from phase 7 (2002–2004) of the Whitehall II study.

Setting: An occupational cohort originally recruited in 1985–1987 was included in the study.

Participants: A total of 2693 men and 977 women had information on cortisol levels and alcohol consumption.

Outcome Measures: Saliva samples were taken on waking, waking + 0.5, 2.5, 8, and 12 h, and bedtime for the assessment of cortisol.

Results: In men there was a positive association between cortisol and units of alcohol intake per week (3% increase in cortisol per unit of alcohol consumed; P = 0.010). The slope of cortisol decline over the day in heavy drinkers was reduced (heavy drinkers β = −0.155, moderate drinkers β = −0.151), indicating reduced control of the HPA axis in heavy drinkers. In women the cortisol awakening response was greater in heavy drinkers 14.15 nmol/liter (9.12–19.17) compared with moderate drinkers 8.69 nmol/liter (7.72–9.67) (P = 0.037).

Conclusions: This study suggests that alcohol consumption is associated with activation of the HPA axis. These results are not due to alcohol consumption on the day, suggesting chronic changes of the HPA axis in heavy drinking groups.