AbstractPhorbol esters are polyfunctional agents which influence the carcinogenic process via a receptor mechanism. Two structural elements of phorbol esters seem to be responsible for tumor promoting activity. One element is formed of certain hydrophilic groups which are supposed to be responsible for the specific receptor binding. The other element consists of hydrophobic groups which should rather unspecifically be responsible for partition and transport between biological phases. In order to differentiate between these two structural elements, the numerical relativ tumor promoting activity of phorbol diesters (a new activity in QSAR) was calculated from rodent skin painting experiments and its dependence from hydrophobicity was modeled using the parabolic and the bilinear model. The results show that the tumor promoting activity of aliphatic phorbol 12,13‐diesters can adequately be described by hydrophobicity only. This indicates that the structural element aliphatic‐12,13‐diesters is rather unspecifically responsible for partition and transport between biological phases. A medium hydrophobicity caused by aliphatic ester chains in position 12 and 13 of phorbol is a sufficient condition for high promoting activity as long as the other hydrophilic groups are not removed, acylated or otherwise ch