T lymphocytes from healthy aged subjects were challenged with 12-O-tetradecanoylphorbol-13-acetate (TPA, a T-cell mitogen) in solid cultures and compared under the same experimental conditions to a group of younger controls. The aged cells showed diminished proliferation and incorporation of tritiated thymidine (3H-Tdr). However, when unfractionated peripheral blood mononuclear cells or isolated T cells from the aged individuals were cultured in the presence of 2-mercaptoethanol, autologous erythrocytes or co-cultured with a non-T cell fraction, an increased proliferative response was observed. Our results suggest that the reduction in proliferative capacity of aged T cells observed in liquid culture is also elicited in solid conditions. However, under appropriate signals a TPA-susceptible T-cell subpopulation may contribute significantly in enhancing their in vitro response. This in turn would suggest that age-related cellular changes are intrinsic in nature and not fully reversible with potentiating factors.