The intestinal absorption of a 19-norprogesterone (ST-1435) was studied in rats after an oral dose of 5 mg ST-1435/kg body weight. Blood samples were collected simultaneously from the portal vein and by cardiac puncture. Plasma ST-1435 concentrations were measured from the samples by radioimmunoassay (RIA). Chromatographic purification of ST-1435 in rat plasma revealed a metabolite cross-reacting in the RIA. A peak concentration of 240 ng ST-1435/ml was found in portal plasma 75 minutes after administration, indicating that the steroid is well absorbed from the small intestine. However, in spite of the relatively high dose used, the plasma concentrations of ST-1435 in the systemic circulation remained low and of short duration. Thus, it seems that ST-1435 in hepatic portal blood is extensively taken-up and metabolized by the liver, resulting in low plasma concentrations of ST-1435 in the systemic circulation when the steroid is administered orally. This is also supported by the observation that higher metabolite levels were found in systemic plasma than in portal plasma during the first 90 minutes after administration. This pronounced first-pass effect may also explain why in women oral administration of ST-1435 has failed to result in any biological effect.