SUMMARYIntroduction. Evaluation ofLeishmaniadrug susceptibility depends onin vitroSb^Vsusceptibility assays, which are labour-intensive and may give a biased view of the true parasite resistance. Molecular markers are urgently needed to improve and simplify the monitoring of Sb^V-resistance. We analysed here the gene expression profile of 21L. braziliensisclinical isolatesin vitrodefined as Sb^V-resistant and -sensitive, in order to identify potential resistance markers.Methods. The differential expression of 13 genes involved in Sb^Vmetabolism, oxidative stress or housekeeping functions was analysed duringin vitropromastigote growth.Results. Expression profiles were up-regulated for 5 genes only, each time affecting a different set of isolates (mosaic picture of gene expression). Two genes,ODC(ornithine decarboxylase) andTRYR(trypanothione reductase), showed a significantly higher expression rate in the group of Sb^V-resistant compared to the group of Sb^V-sensitive parasites (P<0·01). However, analysis of individual isolates showed both markers to explain only partially the drug resistance.Discussion. Our results might be explained by (i) the occurrence of a pleiotropic molecular mechanism leading to thein vitroSb^Vresistance and/or (ii) the existence of different epi-phenotypes not revealed by thein vitroSb^Vsusceptibility assays, but interfering with the gene expression patterns.