To investigate human isotype expression among lymphocyte populations, we have studied IgG subclass production by splenocytes, tonsil cells, and peripheral blood lymphocytes (PBL) after stimulation with a panel of nine mitogens. Response magnitudes varied with tissues: all mitogens produced the strongest responses with splenocytes and the smallest with PBL. In addition, the IgG subclass maximally stimulated by a particular mitogen also depended on the tissue studied. For example, LPS mainly stimulated IgG2 in PBL and IgG1 in spleen. Interestingly, the response patterns seen in splenocytes suggest a large and coordinate expression of IgG1 and IgG3 subclasses. Implications of these findings are discussed with respect to immunoglobulin gene organization and human disease states.