Previous studies from our laboratory have shown that large granular lymphocytes (LGL) mediate natural killer cell (NK) activity in dogs and that host LGL are associated with graft failure in a canine model of histoincompatible marrow transplantation. We now report studies on the effects of anti-CD18 monoclonal antibody (MAB) 60.3, ultraviolet (UV) irradiation and cyclosporine (CSP) on in vitro canine NK function. Treatment with the murine anti-CD18 MAB 60.3 produced marked diminution in lytic function (mean 79% inhibition). UV irradiation at doses greater than 1.6 millijoules/cm2 completely eliminated NK function; this effect was not due to defective effector/target conjugate formation. CSP also inhibited NK function, although in vitro lytic activity was not completely blocked (mean of 44% inhibition) at concentrations which correspond to those achieved in vivo (400 ng/mL). These observations form a basis for future investigations aimed at preventing graft failure in the canine model of histoincompatible marrow transplantation by blocking NK function in vivo.