A series of colloid silver or gold nanoparticles (AgNPs or AuNPs) were successfully prepared by in situ reduction and stabilization of hyperbranched poly(amidoamine) with terminal dimethylamine groups (HPAMAM-N(CH(3))(2)) in water, and they all exhibited highly antimicrobial activity. The particle size could be controlled easily by adjusting the molar ratio of N/Ag (or N/Au) in feed. When the molar ratio was 2, some aggregates of the nanoparticles separated from the colloidal solution, which showed some limited antimicrobial activity with the bacterial inhibition ratio of below 15%. As the molar ratio increased from 10 to 30, the average particle diameters decreased (from ca. 7.1 to 1.0 nm for AgNPs and from ca. 7.7 to 3.9 nm for AuNPs, respectively) and they all showed high dispersion stability and excellent antimicrobial efficiency. All the bacterial inhibition ratios reached up to ca. 98% at the low silver content of ca. 2.0 microg/mL or at the low gold content of ca. 2.8 microg/mL. The AgNPs or AuNPs with smaller particle size can provide much more effective contact surface with the bacteria, thus enhancing their antimicrobial efficiency. Besides, the cationic HPAMAM-N(CH(3))(2) can also do some contribution to the antimicrobial activity through the strong ionic interaction with the bacteria.