A 200 mg dose of micronized progesterone (P) was administered orally to six healthy volunteers. Serial blood samples were collected and plasma P was assayed according to three methods of different specificity. The results were compared to those obtained with a reference technique based on gas chromatography-mass spectrometry. The interference of P metabolites particularly 5 alpha- and 5 beta-dihydroprogesterone was shown to be important when no or inadequate chromatography was included in the method. Radioimmunoassay after chromatography on a Celite column yielded results similar to those of the reference method. After oral administration, plasma P reached a peak at 3.00 +/- 0.44 h (mean +/- SEM; range: 1-4 h). The mean peak level 4.70 +/- 1.15 ng/ml (mean +/- SEM; range: 2.40-10.10 ng/ml) was at the lower limit of the range defined for a normal functional corpus luteum. The levels returned to initial values by 24 h after the single oral dose. The separation of P from its metabolites by an adequate chromatographic system appears mandatory after oral administration of micronized P.