Four new members of the SOCS family of molecules in rainbow trout (Oncorhynchus mykiss), CISH and SOCS6, 7 and 9, are described for the first time in this species. The genes had a wide tissue distribution in trout, and were detected in gills, skin, muscle, liver, spleen, head kidney, intestine and brain, with brain having the highest expression levels. Stimulation of a rainbow trout leucocyte cell line, RTS-11, (mononuclear/macrophage-like cells) with LPS or Poly I:C had no effect on the expression of these genes, although in both cases the previously identified SOCS1-3 genes were up-regulated. Similarly, stimulation of RTS-11 or RTG-2 (fibroblasts) cells with the trout recombinant cytokines IFN-gamma or IL-1beta had no effect on CISH or SOCS6, 7 and 9 expression. However, PMA stimulation did impact on SOCS6 and SOCS9 expression, and LPS stimulation of primary cultures or bacterial infection (Yersinia ruckeri) increased significantly CISH expression (as well as SOCS1 and SOCS2 or SOCS3 respectively). It is apparent that the type II SOCS genes (CISH, SOCS1-3) are particularly relevant to immune regulation in fish, although the intriguing expansion of the SOCS4/5 subgroup in fish requires further investigation as to their role and functional divergence.