Sesquiterpene lactones are known for their anti-inflammatory activity which has been proven in various assays on DNA, mRNA and protein level. Here we report on the change in the gene expression profile in TNF-alpha stimulated human 293 cells after treatment with parthenolide using a cDNA microarray analysis. Twenty-one of 7028 genes were found to be up- and 18 down-regulated. They encode for chemoattractants, immune system proteins, glycoproteins, metabolism, serine proteinases, and transcription factors. Confirmatory analyses were carried out using quantitative real-time RT-PCR (TaqMan). Additional studies with selected genes revealed the concentration-dependent influence of parthenolide on the expression of these genes.