Two lines of chickens, derived by two-way selection for either a high (HPC) or low (LPC) plasma corticosterone response to social stress, were inoculated with Marek's disease virus (MDV). Lymphocyte transformation (LT) microassays were performed to assess the CMI response of leucocytes from HPC and LPC MDV-infected chickens. Blastogenesis was quantitated by ³H-thymidine uptake. Leucocytes from chickens specifically sensitized with either heat-killed tuberculin or 1,5-di-fluoro-2,4-dinitrobenzene were subsequently stimulated in vitro with either purified protein derivative (PPD) or dinitrophenyl-bovine serum albumin (DNP-BSA) conjugate. Phytohemagglutinin (PHA-P) was used to assess non-specific lymphocyte transformation. MDV-infected HPC and LPC chicken leucocytes were also compared for their ability to lyse ⁵¹Cr-labeled fowl erythrocytes upon stimulation with PHA-P. Leucocytes from non-infected LPC control chickens underwent blastogenesis to a greater extent than did non-infected HPC control chickens. Although all tumor-bearing chickens demonstrated a markedly suppressed LT response, LPC chickens demonstrated a greater LT response than did HPC chickens. Relative to steroid level chickens infected with MDV, but without tumors, demonstrated a suppressed LT response; however, this response was greater than that of chickens with tumors, but less than that of normal controls. Under conditions of sustained high social stress, HPC chickens demonstrated a decreased cell-mediated cytotoxicity (CMC) in comparison with LPC chickens. In both steroid lines, CMC decreased with the onset and severity of tumors. The impaired CMI seen in the HPC line corresponded with an increased tumor incidence and a greater mortality in this line than in the LPC line. Metyrapone, a chemical which blocks adrenal corticosterone synthesis, transiently enhanced CMC and initiated tumor regression in birds debilitated with MD tumors. Early treatment with 500 ppm metyrapone mixed in feed was most effective. / M.S.