Sera from nine men and one woman having the recently described acquired immunodeficiency disease syndrome (AID) were studied for effects on healthy control lymphocyte activationin vitro by two T-lymphocyte activators, phytohemagglutinin (PHA) and allogeneic lymphocytes in the mixed lymphocyte culture (MLC) reaction. Selected sera were also tested for blocking of endogenous natural killer (NK) activity against the K562 tumor target. The results obtained demonstrated that all of the sera tested had a strong capacity to block the normal T-cell response and that this blocking effect could be diluted out. Some of the sera blocked -interferon (IFN)-induced NK activity but not endogenous NK activity. All of the patients had abnormal lymphocyte responses to T-cell activators in pooled normal human serum-supplemented cultures. There was no simple correlation between patient lymphocyte deficiency and percentage blocking capacity of patient serum. Sera were absorbed against sheep red blood cells (SRBC) and against allogeneic cells. SRBC absorption was effective in removing serum factors blocking normal lymphocyte responses to PHA and, in some cases, to allogeneic cells, whereas allogeneic absorption did not prevent serum inhibition of the PHA response. Conversely, allogeneic absorption removed serum factors blocking normal responses in MLC at least as well as or better than SRBC absorption. Increasing the number of absorptions increased the efficacy of allogeneic absorption. The positive effect of allogeneic absorptions was observed only when the stimulating allogeneic cell pool in the MLC was the same pool as that used in absorptions. The results suggest that both anti-T lymphocyte- and anti-major histocompatibility complex (MHC)-linked determinants are present in the sera of patients with AID. The implications of these findings are discussed.