Spontaneous production of autoantibodies to the Sm nuclear Ag is highly specific for SLE and the SLE-prone MRL mouse strains. Our previous studies have demonstrated that in vitro anti-Sm production in MRL/1pr mice requires the presence of T cells. In the present investigation, these T cells were found to express the L3T4+/Lyt-2- phenotype, unlike the aberrant L3T4-/Lyt-2-"double negative" 1pr T cells, and to utilize the L3T4 determinant in generating help for the anti-Sm response. The generation of anti-Sm did not require the presence of Sm-specific Th cells, as help could also be provided by T cells activated to an irrelevant Ag, or by nonspecific factors such as IL-2. There was no evidence for suppressor cell regulation of anti-Sm, even in animals negative for this specificity. These studies indicate that ongoing production of anti-Sm in MRL/1pr mice is dependent on the presence of T cells with a normal mature surface phenotype, and that these cells act in part through the elaboration of lymphokines. They further show that the anti-Sm status of individual MRL/1pr mice is not due to the action of suppressor cells. Because T cells appear to act primarily in a permissive fashion for the anti-Sm response, it is likely that events underlying the initial generation of Sm-specific B cell precursors are critical in determining whether an individual animal develops the Sm serologic specificity. Once these cells have arisen, clonal expansion of Sm-specific B cells may proceed in the presence of activated T cells or some of their products.