The design and synthesis of a family of cationic, pH-sensitive poly(amidoamine)s are reported. Acetal or ketal linkages were incorporated into the backbone of the polymers to provide for degradation into low molecular weight hydrophilic compounds upon lowering of the pH. All of the polymers demonstrated a pH-dependent degradation profile with a very significant increase in hydrolysis rate as the pH was lowered from 7.4 to the pH value of 5.0 commonly found in lysosomes. The hydrolysis half-life of the poly(amidoamine)s varied from 0.03 to 81.5 days at pH 5.0 and from 6.0 to 161 days at pH 7.4, depending upon the structure of the components used to prepare each of the acid-degradable polymers. This data suggests that these new pH-sensitive hydrophilic poly(amidoamine)s and analogous structures may prove useful in the field of polymer therapeutics and drug delivery.