In an effort to isolate genes that change expression at the mRNA level during treatment of fibroblast-like synoviocytes (SFC) with IFN-gama, we performed a differential display analysis. Here, we report the isolation of a cDNA clone corresponding to a 3.1 kb mRNA species that is reduced in synoviocytes after culture with IFN-gama. Sequence analysis revealed the 211 bp length cDNA clone to be identical to the motility-stimulating 125 kDa protein autotaxin (ATX). The down-regulation of ATX mRNA was confirmed by Northern blot analysis as well as competitive RT-PCR. SFC express 1 ng ATX mRNA/microgram total RNA. IFN-gama down-regulated ATX mRNA up to 50% as compared to control. Our results add a new finding to the manifold functions described for IFN-gama in rheumatoid arthritis.