A method using gold nanoparticles (GNPs) to enhance fiber optic interferometry (GNPFOI) for immune-sensing is reported in this paper. It is suggested that an enlarged index mismatch and an elongated optical path by GNPs conjugated on recognition proteins will contribute most to signal enhancement in the interference fringe shift. Theoretical and experimental results show that the interference fringe shift is linearly related to both the amount and size of the GNPs binding on the sensor surface. The detected signal for 30 nm GNPs can reach a lowest detection limit of 18 pM (10(10) particles ml(-1)). Immune-sensing for rabbit IgG as the antigen to anti-rabbit IgG has been demonstrated and a detection cycle has been completed by elution buffer for surface regeneration. The repeatability of the immune-sensing on one GNPFOI sensor has also been verified by three identical cycles, and the detection limit for 13 nm GNPs conjugated anti-rabbit IgG reaches 0.17 nM (∼25.5 ng ml(-1)). The sensory mechanism has the potential to be engineered on the tip of a needle-type micro-device, which would allow it to monitor immune recognition signals in the future.