A micromachined PZT (52/48) thin film cantilever composed of SiO2/Ta/Pt/PZT/Pt/SiO2 on a SiNx supporting layer for simultaneous self-exciting and sensing was fabricated. We present the resonant frequency change of piezoelectric microcantilevers due to a combination of mass loading and spring constant variation arisen from antigen-antibody interaction of C-reactive protein (CRP). Experimentally measured resonant frequency shift is larger than that of theoretically calculated resonant frequency by two orders of magnitude due to a compressive stress arising from CRP antigen-antibody interaction. The changes in normalized resonant frequency shift δf expt/f1 expt were found to increase as the value of 40.5, 74.7, and 185×10-4 as the CRP antibody site ratio, increased 10%, 50%, and 100%, respectively. © 2004 American Institute of Physics.