Prolonged administration of vitamin A to guinea pigs caused lymphomonocytosis and marked changes in organs of the lymphomyeloid complex, with proliferation of atypical mononuclear cells in the spleen, lymph nodes, and liver. In the bone marrow, atypical mononuclear cell proliferation was also encountered and represented 13% of the entire marrow cell population in some animals. Electron microscopic examination of the marrow revealed many lymphocytes and plasma cells with a well-developed rough endoplasmic reticulum (RER), suggesting that these cells are active in protein synthesis and antibody production. The atypical mononuclear cells described appeared to belong to the monocytic series and contained a variety of dense bodies, and a well-developed RER and Golgi apparatus. Vitamin A is mitogenic, labilizes lysosomal and cell membranes, and can act as an adjuvant enhancing immune responses. It has been suggested that vitamin A alters lymphoid cell membranes and enhances the degree of immune response by stimulation of cell division in immunologically competent cells. The lesions described here may well be the morphologic counterpart of an enhanced cellular immune response.