We have examined the carrier-specific helper activity of a number of antigen-specific, I region-restricted T cell hybridomas prepared in our laboratory. The hybridomas were assayed for helper activity in the presence or absence of exogenously added nonspecific factors found in the concanavalin A-activated supernatants of normal mouse spleen cells. Of six hybridomas tested, all six could stimulate the IgM anti-hapten response of hapten-primed B cells in the presence of the appropriate hapten-carrier conjugates. At low or moderate carrier doses, the response was dependent upon hapten-carrier linkage and the ability of the hybridoma cells to interact with carrier in association with H-2 products of the responding B cells themselves. Plaque-forming cell responses stimulated by some of the hybridomas were absolutely dependent upon the addition of nonspecific factors, suggesting that anti hapten-protein responses require both an antigen specific I region restricted signal from the T cell hybridomas and nonspecific helper factors, made either by the T cell hybridomas or added exogenously. Under two sets of circumstances, B cells were stimulated in the absence of a simultaneous signal delivered through their immunoglobulin receptor. This occurred either when hapten-primed B cells were stimulated with an ovalbumin/I-Ak-specific hybridoma in the presence of very high concentrations of ovalbumin, or when H-2b B cells were incubated with a hybridoma specific for I-Ab alone. This was interpreted to mean that B cells can be stimulated by reaction of T cells with surface I molecules.