We investigated the capacity of anti-Ia monoclonal antibody Fab and Fab'2 fragments to inhibit keyhole limpet haemocyanin (KLH) or concanavalin A (Con A)-induced T-cell proliferations. Both types of fragments of anti-I-Ak and anti-I-E/Ck monoclonal antibodies inhibited these responses. On a protein concentration basis, the inhibitory effects of fragmented antibodies were less pronounced than those of undigested molecules. However, once the differences in antigen-binding capacity were compensated, antibody fragments were as efficient inhibitors as undigested molecules. These results suggest (i) that masking of Ia antigenic determinants is the essential mechanism of anti-Ia antibody-mediated inhibitory effect; (ii) that some KLH-specific proliferating T lymphocytes are I-E/Ck restricted; (iii) that the Ia antigen role is not limited to restriction of cell interactions since the Con A-induced proliferation, a non-H-2 restricted response, is inhibited by anti-Ia Fab fragments.