Guinea pigs were immunized with liposomal model membranes actively sensitized with 2,4-dinitrophenyl-aminocaproylphosphatidyl-ethanolamine. The immune response was characterized by the formation of both IgM and IgG anti-DNP plaque-forming cells (PFC) which paralleled the appearance of anti-DNP antibodies in the serum. Plaque inhibition by DNP-lysine indicated that the PFC produced after liposomal immunization fell in a much narrower range of avidity groups than the PFC obtained after immunization with DNP-albumin and, in this regard, resembled MOPC 315. The restricted nature of the serum IgG anti-DNP antibodies was confirmed by isoelectric focusing and revealed the expression of a limited number of clones in all cases.