The precise mechanism(s) of immunological tolerance to both self-and non-selfantigens remains unclear, despite substantial advances in the understanding of cellular and molecular immunology over the past three decades. Current hypotheses may be divided into two broad (but not necessarily mutually exclusive) categories: (a) those involving direct, antigen-induced clonal inactivation of specific T and/or B cells, and (b) those in which suppressor T cells (Ts) 1 are held to be responsible for specific unresponsiveness. The first category includes classical clonal deletion as described originally by Burnet (1) and modified subsequently by Bretscher and Cohn (2) in their "two signal" hypothesis. According to the latter, contact of an antigen-reactive cell with antigen alone (signal one) in the absence of a second triggering signal from a collaborating cell (signal two) leads to irreversible inactivation of the cell concerned. Related to this are certain variations (3, 4) of Lederberg's original hypothesis of selftolerance (5) which stated that developing lymphocytes are more sensitive than mature cells to antigen-induced inactivation. In some in vitro models receptor blockade has also been invoked as a mechanism for clonal inactivation (6), although this appears to be reversible (7) and its significance in vivo is uncertain.In the second category of hypotheses, antigen-specific (or in some cases idiotypespecific) suppressor cells are held to be responsible for initiating and maintaining tolerance. Although Ts have been shown to be present in a wide variety of unresponsive states (8-13), their precise role in the induction and/or maintenance of unresponsiveness remains controversial. One of the major reasons for this uncertainty is the repeated observation that the kinet.ics and magnitude of suppressive activity do not parallel the time course and degree of tolerance (14-16). Thus some investigators have come to regard the presence of Ts as a regulatory epiphenomenon of little or no relevance to the mechanism of immunological unresponsiveness (15,17,18).In this communication, Ts specific for the protein antigen human gamma globulin (HGG) have been shown to exist in two distinct functional states in tolerant animals, effector cells and memory cells. The activity of the former is readily apparent in standard adoptive mixing experiments shortly after tolerance induction, but their *