Activated B cells isolated shortly after primary immunization of BALB/c donor mice with sheep erythrocytes (SRBC), were transferred to normal syngeneic recipients or to low-dose cyclophosphamide-pretreated syngeneic recipients. In pretreated recipients, the transfer of activated B cells, but not of T cells or macrophages, resulted in an augmented production of indirect plaque-forming cells in the primary immune response to SRBC but not to horse erythrocytes. It was shown in double-transfer experiments that T helper cells (Lyt-1+) had been stimulated by the transfer of antigen-activated B cells. Criss-cross double-transfer experiments using the mouse strains CB20 and BAB14 (congenic to BALB/c at the loci coding for the immunoglobulin heavy chain) indicate that those T helper cells are primed after recognition of B cell products that are encoded for by genes linked to the loci coding for the variable region of the immunoglobulin heavy chain (IgVH). The thus-primed Ig-dependent T helper cells (THIg) are adaptively restricted to cooperate with B cells that display IgVH-linked gene products similar to those that originally stimulated the THIg. These findings suggest that in the course of an immune response to T cell-dependent antigens, help for the production of specific IgG can be provided by THIg that have been primed and/or clonally expanded after recognition of IgVH-linked gene products by (e.g., complementary) T cell receptors.