Although the majority of severe combined immune deficiency (scid) mice lack functional lymphocytes, some (2-23%) appear to develop a limited number of B and T cells between 3 and 9 mo old. Most of these leaky scid mice were shown to contain very few clones (less than or equal to 3) of Ig-producing plasmacytes. Clonal progeny were distributed unevenly in the lymphatic tissues and appeared as discrete plasmacytic foci. In many cases, individual clones persisted for several months and produced abnormally high concentrations of Ig that included multiple isotypes. Functional T cells were inferred from the ability of leaky mice to reject allogeneic skin grafts, a T cell-dependent reaction. Interestingly, approximately 40% of leaky mice developed thymic lymphomas. In other respects, leaky mice resembled regular scid mice; e.g., their splenic cells failed to express common lymphocyte antigens (Ly-5[B220], Ly-1) and to proliferate in response to lymphocyte mitogens. Histologically, their lymphoid tissues retained the same general pattern of severe lymphocytic deficiency as scid mice.