Metabolite assessment is an open question in bioequivalence studies. In situations of low absorption, high first-pass metabolism, and intrasubject variability, metabolites may reflect absorption more adequately than the parent drug, and their determination may help decision-making in bioequivalence issues. Treating alpha-dihydroergocryptine (DHECT) as a model, we used both unchanged DHECT and a pool of DHECT metabolites to evaluate the bioequivalence of 2 oral DHECT formulations (reference-R and test-T) in 12 subjects. DHECT and its metabolites were immunoassayed. There was no difference between the 2 formulations in terms of the AUC0-infinity (area under the curve) values determined from unchanged DHECT or DHECT with metabolites profiles: 572 +/- 490 pg/ml.h (R) and 442 +/- 276 pg/ml.h (T) for unchanged DHECT, and 7,141 +/- 2,936 pg/ml.h (R) and 6,941 +/- 1,462 pg/ml.h (R) for DHECT with metabolites. Confidence intervals were within the ranges 0.8-1.25 (AUC0-infinity) and 0.7-1.43 (Cmax) for DHECT with metabolites but not for unchanged DHECT. This study describes a particular case where only measurements on the basis of the metabolites can justify the assumption of bioequivalence.