In vitro cytotoxicity mediated by killer (K) cells and natural killer (NK) cells post-sheep-pox virus (SPV) infection and immunization in ovines was studied by 51 chromium release lyric assay, The secondary lamb testicular (SLT) and vero cells (VC) infected with respective adapted sheep-pox virus and labelled with radioisolope were used as targets. Maximum NK activity was observed at day 14 post-infection and day 21 post-vaccination, The maximum K cell activity was seen at day 14 post-vaccination/infection, With SLT target using 100:1 effector target (FT) ratio, the per cent cytotoxicity was 72.55 and post-infection 85-48. In vaccinated animals the per cent cytotoxicity was 59.94 and 81.45 respectively.