A diet high in fat has been linked to prostate cancer, possibly through an influence on hormones. Sex hormone-binding globulin (SHBG) binds androgens and is regulated in part by insulin. Diet and exercise can modify insulin levels, potentially affecting SHBG and the biologically available levels of androgens. To determine the effects of a low-fat (< 10% of calories), high-fiber diet plus daily exercise on insulin, SHBG, prostate-specific antigen (PSA), and serum lipids, we measured the levels of these factors in the serum of 27 obese men undergoing a three-week diet-and-exercise program. Insulin decreased from 222 +/- 30 to 126 +/- 21 pmol/l (p < 0.01), and SHBG increased from 18 +/- 2 to 25 +/- 3 nmol/l (p < 0.01). Body mass index decreased from 35 +/- 1.9 to 33.4 +/- 1.8 kg/m2 (p < 0.01). PSA levels were normal and did not change significantly, although in a small subset of men (n = 3) with slightly elevated PSA levels (> 2.5 ng/ml) all showed a decrease. The three-week diet-and-exercise intervention decreased insulin and lipid levels while increasing SHBG. The increase in SHBG would result in more testosterone being bound and, therefore, less of the androgen available to act on the prostate. The decrease in insulin might also decrease mitogenic activity in the prostate. The diet-and-exercise regimen did not have a significant impact on normal PSA levels. Although modest, these changes may be protective against the development of prostate cancer.