Although a variety of disorders are associated with polycystic ovarian disease (PCOD), obesity, hirsutism, and menstrual dysfunction are the most frequent manifestations. We investigated the possibility that obesity per se may give rise to androgen excess through alterations in estrogen metabolism and, consequently, through alterations in gonadotropin secretion. Eighteen obese, infertile women with PCOD were compared with 20 control women. Plasma androstenedione (A) was 252 +/- 18 ng/dl (mean +/- standard error of the mean [SEM]) in the obese women compared with 173 +/- 9 ng/dl in the controls (P less than 0.001); plasma testosterone (T) was 66 +/- 5.7 ng/dl, compared with 41 +/- 3 ng/dl (P less than 0.001). Thirteen of the obese women lost greater than 15% of their body weight by dietary restriction; ten of these women (77%) conceived spontaneously. In seven of the ten women who conceived, we remeasured plasma androgens following weight reduction but prior to conception. A decreased from 295 +/- 19 ng/dl to 179 +/- 5 ng/dl; T decreased from 75 +/- 8 ng/dl to 39 +/- 5 ng/dl (P less than 0.001). We conclude that obesity may play a role in the genesis of PCOD.