The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited because of hepatic breakdown of the ingested androgens. Because androstenediol administered sublingually with cyclodextrin bypasses first-pass hepatic catabolism, we evaluated the acute hormonal response to sublingual cyclodextrin androstenediol supplement in young men. Eight men (22.9 ± 1.2 yr) experienced in strength training consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (Sl Diol) or placebo (Pl) separated by at least 1 wk in a randomized, double-blind, crossover manner. Blood samples were collected before supplementation and at 30-min intervals for 3 h after supplementation. Serum hormone concentrations did not change with Pl. Serum androstenedione concentrations were increased (P < 0.05) above baseline (11.2 ± 1.1 nmol/l) with Sl Diol from 60 to 180 min after intake and reached a peak concentration of 25.2 ± 2.9 nmol/l at 120 min. Serum free testosterone concentrations were increased from 86.2 ± 9.1 pmol/l with Sl Diol from 30 to 180 min and reached a peak concentration of 175.4 ± 12.2 pmol/l at 60 min. Serum total testosterone concentrations increased above basal (25.6 ± 2.3 nmol/l) from 30 to 180 min with Sl Diol and reached a peak concentration of 47.9 + 2.9 nmol/l at 60 min. Serum estradiol concentrations were elevated (P < 0.05) above baseline (0.08 ± 0.01 nmol/l) from 30 to 180 min with Sl Diol and reached 0.14 ± 0.02 nmol/l at 180 min. These data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, total testosterone, and estradiol concentrations.