The protonation mechanisms of the poly(amidoamine) (PAMAM) andpoly(propyleneimine) (PPI) dendrimers are clarified and related to their molecular structure. The overall proton binding isotherms can be interpreted in terms of a site binding model, which involves a limited number of parameters, and can be used to gain detailed insight in both macroscopic and microscopic protonation mechanisms. The protonation of the PAMAM dendrimers is dominated by the chemical environment of the amine sites, and the sites protonate almost independently leading to protonation mechanism with a characteristic intermediate core-shell structure. In the case of PPI, the protonation is dominated by the electrostatic nearest-neighbor repulsions between the protonated sites, and leads to an intermediate »onion-like« structure where all the odd shells are protonated. Copyright of Croatica Chemica Acta is the property of Croatian Chemical Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.