Cytotoxic cells isolated from the head kidney and peripheral blood of the channel catfish appear to represent distinct subpopulations of effector cells, Previous studies showed that the former lyse xenogeneic natural killer (NK) cell targets, whereas the latter preferentially lyse allogeneic cells. Here we extend these studies and present data suggesting a third class of cytotoxic effecters responsible for killing virus-infected allogeneic and autologous cells, Peripheral blood leukocytes (PBLs) freshly isolated from unimmunized catfish lyse uninfected allogeneic target cells as well as virus-infected allogeneic and autologous cells, Cell depletion and unlabeled (''cold'') target inhibition studies discriminated between putative effector classes and supported the view that at least two populations of cytotoxic cells are present within peripheral blood leukocytes. One population lyses allogeneic targets, whereas a second population kills channel catfish virus (CCV)-infected cells, In addition, inhibitor studies demonstrated that early virus gene products are sufficient to render infected cells susceptible to lysis, These results suggest that channel catfish possess distinct populations of NK-like, PBL-derived cytotoxic cells capable of lysing allogeneic and virus-infected target cells. Copyright (C) 1996 Elsevier Science Ltd.