Summary. Antithrombin III (AT III) activity has been measured in 9669 healthy blood donors (5525 male and 4144 female). The distribution of AT III is approximately ‘normal’ with mean 105·6 iu/dl and standard deviation 11·2; however, definite age and sex related variations are evident. Pre-menopausal females have lower mean AT III compared to their male contemporaries who have remarkably stable mean AT III until 45 years, after which there is a gradual decline. In contrast, post-menopausal females have higher mean AT III than both males of the same age and younger pre-menopausal females. Concurrent hormone replacement therapy inhibits this rise. The use of hormonal preparations is associated with a 4 iu/dl reduction of mean AT III in younger females but not in those over 30 years. Smoking may result in a mild increase in AT III of doubtful clinical significance. On-going genetic and family studies are expected to predict a prevalence rate of congenital AT III deficiency in excess of the previously reported figure of 0·02%. The authors consider these observed variations as minor and recommend the use of a single reference range for AT III activity, but that particular care be taken when interpreting results in pill-taking females and the elderly.