Monoclonal antibodies (MAbs) raised against porcine adipocyte plasma membranes were used to demonstrate complement-mediated cytotoxicity of adipocytes and preadipocytes in primary stromal-vascular (SV) cultures. Five of the six MAbs tested significantly reduced the number of fat cell clusters in cultures maintained in medium supplemented with pig serum and dexamethasone (PS/DEX) but not in cultures supplemented with insulin, transferrin, and selenium (ITS). Neither MAb nor complement alone affected fat cell cluster number. Treatment of both ITS and PS/DEX cultures with pools of 2 or more MAbs, in combination with complement, eliminated fat cell clusters in all instances. Treatment of cultures prior to appearance of cells containing lipid demonstrated that preadipocytes, or adipose lineage cells, could also be eliminated by MAb/complement treatment. Finally, injection of young rats with a pool of three of the MAbs produced a 30% reduction in inguinal fat pad weight without affecting other tissues. Adipocyte/preadipocyte-depleted cultures can now be used as a model system to examine progression of cells through the adipose cell lineage at a time not previously possible with primary cells.