The relationships between certain reproductive, demographic, and medical variables and the carpal tunnel syndrome were examined using data from a hospital-based case-control study of women ages 45 to 74 years in the New Haven and Hartford, Connecticut, areas from 1977 to 1979. Characteristics of 40 carpal tunnel syndrome cases and 1,043 controls from hospital surgical services were compared. A history of diabetes was associated with an increased frequency of occurrence of the carpal tunnel syndrome, a finding consistent with clinical observation. Recent weight gain and use of estrogen replacement therapy were identified as possible risk factors; this provides some support for the theory that fluid retention in the soft tissues of the carpal tunnel is etiologically involved, although these results are preliminary and further research must be carried out to refute or support these findings. The negative association of the carpal tunnel syndrome with height and a history of varicose veins and the positive association with age at menopause cannot be explained and need verification.