A homeopathic widespread belief is that the inversion of effect of the drugs in homeopathic medical practice is due to dilution or very low doses, but there are many homeopathic incoherencies. For example the first conception of the similia principle was obtained through planned, small sample, clinical experiments with ponderal/pharmacological doses in healthy and diseased subjects1. Furthermore the classical foundations of the similia principle in Organon2, the primary and secondary actions of drugs, were thought to be connected with opposite, time-dependent reactions of the body to high doses and the inversion of effect was seen in temporal sequence after a strong dose and not after changes of doses, so the idea that dilutions are responsible for inversion of effects is not suitable to the classical theory. And lastly homeopathic provings or pathogenetic trials have frequently mixed, unregarded to the doses, occasional toxicological symptoms and symptoms obtained through diluted substances3, reinforcing the idea that, on healthy subjects, in several cases many substances produce the same symptoms in pharmacological or infinitesimal doses. So at least the dose-dependent inversion of effect is not generalized in a great part of the collected symptoms. Biological foundations to similia principle have to be searched in other directions4, as in different sensitivity to drugs between health and disease, or in different time-dependent effect of drugs on specific, but different, cell sensitivity set point. In the vision described here both these possibilities represent the same phenomenon of altered cell sensitivity. It is aim of this article to show that the original hahnemannian idea to explain homeopathic similia principle starting from a pharmacological and biological point of view with ponderal doses, seems correct, rationally comprehensible and based on modern knowledges. The three pharmacologic examples that best illustrate this reasoning, coffe, opium and wine, will be discussed.