Specific phorbol ester receptors are found in the particulate fraction of cells. In addition, cytosol contains a phorbol ester apo-receptor, which requires phospholipids for reconstitution. The apo-receptor corresponds to protein kinase C, and the quantitatively major membrane receptor appears to be a protein kinase C-phospholipid complex. The ability to reconstitute the phorbol ester apo-receptor into different lipid domains permits analysis of the role of the lipid domain in phorbol ester receptor function. Studies reviewed here indicate that diacylglycerols competitively inhibit phorbol ester binding, consistent with their being the postulated endogenous phorbol ester analogs. Highly lipophilic phorbol esters only inhibit effectively if incorporated into the lipid phase, indicating that the membrane dissolved form of the ligand can be recognized. The binding affinity of [3H]phorbol 12,13-dibutyrate for holo-receptor depends markedly (greater than 20-fold range) on the phospholipid environment, and heterogeneous phorbol ester binding (i.e., curved Scatchard plots) can be generated by use of heterogeneous lipid environments in the reconstitution. The possible existence of other phorbol ester receptors in addition to protein kinase C-phospholipid complexes remains to be resolved.