Sex hormones may influence risk factors for noninsulin-dependent diabetes mellitus (NIDDM). Decreased sex hormone-binding globulin (SHBG; an indirect measure of androgenicity) is associated with hyperinsulinemia and insulin resistance. We measured SHBG concentrations in 58 subjects who later converted to diabetes and 107 subjects who remained normoglycemic throughout the 8 yr of follow-up of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Among premenopausal women, SHBG concentrations (nanomoles per L) were significantly lower in converters than in nonconverters (41.6 +/- 12.4 vs. 74.4 +/- 10.0; P = 0.004), but corresponding differences were not observed in postmenopausal women or in men. Since, however, analysis of variance suggested no significant interaction between menopausal status and conversion to NIDDM, we pooled pre- and postmenopausal women. Subsequent analysis indicated that SHBG concentrations predicted the development of NIDDM in women independently of glucose and insulin concentrations. We conclude that increased androgenicity, as assessed by decreased SHBG concentrations, is an important independent risk factor for NIDDM in women.