In order to study the relationship between plasma sex-hormone-binding globulin (SHBG) and insulin levels in healthy women, we investigated the association between plasma SHBG and insulin in an occupational sample of 786 nonhormone-using women. Levels of plasma SHBG showed a stepwise decrease with increasing fasting plasma insulin in premenopausal as well as in postmenopausal women. In these cross-sectional data, this significant negative relationship between SHBG and insulin was shown to be independent of age, body mass index, subscapular skinfold, fasting and 2-h plasma glucose in both groups. The etiology and the consequences of this inverse association between SHBG and insulin are unclear. Prospective and clinical studies in women will be necessary to determine the direction and causal nature of the association between SHBG and insulin, as well as its mechanism and its physiological and/or pathophysiological consequences.