Testosterone (T) is not administered orally because it has been reported to be rapidly metabolized by the liver. We hypothesized that sufficient doses of T or T enanthate (TE), administered orally in oil, would result in clinically useful elevations in serum T. We also hypothesized that co-administration of dutasteride (D) with the T or TE would minimize increases in serum DHT seen previously with oral administration. Therefore, we conducted a pharmacokinetic study of oral T and TE in oil, with and without concomitant D, in normal men whose T production had been temporarily suppressed by the gonadotropin-releasing hormone (GnRH) antagonist acyline. Thirteen healthy men, (mean age 24 ± 6 yr), were enrolled and assigned to oral T (n = 7) and oral TE (n = 6) groups and were administered 200, 400 or 800 mg of either T or TE in sesame oil in the morning on 3 successive days 24 h after receiving acyline. Blood samples for measurement of serum T and DHT were obtained before T or TE administration and 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h after administration. Subjects were then administered D for four days before repeating the sequence of T or TE doses with D. Serum T was significantly increased in a dose-dependent fashion with the administration of oral T or TE in oil. Co-administration of D with oral T or TE significantly increased the 24-hour average serum T levels compared with administration of T or TE alone (average serum T after 400 mg dose: 8.7 ± 3.0 nmol/L (T) and 8.3 ± 5.7 nmol/L (TE) vs. 16.1 ± 5.8 nmol/L (T +D) and 15.0 ± 8.8 nmol/L (TE + D); P < 0.05 for T vs. T + D]. The administration of oral T or TE in oil combined with D results in unexpected and potentially therapeutic increases in serum T. Additional studies of this combination as a novel form of oral androgen therapy are warranted.