the determination of their uptake, accumulation, detoxification, and excretion processes of these species [7] would be significant for better understanding and handling mercury poisoning. [8] The current methods to monitor Hg(II) and MeHg are mostly based on indirect detection after time-consuming pretreatment and tedious separation, such as cold vapor atomic absorption spectroscopy, inductively coupled plasma optical emission spectrometry (ICP-OES) and inductively coupled plasma mass spectrometry (ICP-MS). [9,10] In addition, mercury speciation varies dramatically in different aqueous solutions. [11,12] These factors make the in vivo and realtime examination of both ions difficult. Fluorescence (FL) imaging, an important imaging method for biological samples, [13,14] offers powerful reagents to interrogate the physiology and pathology on species in their native environments with minimal perturbation to living systems. [15-17] Therefore, the ideal pathway for the in vivo detection of Hg(II) or MeHg could be FL imaging by dualresponse probes, [1,18-23] with biocompatibility and infrared (near-infrared)-emitting properties. [24-35] Nevertheless, previously reported probes always showed Hg(II) and MeHg emission at the same wavelength, [36] making simultaneous in vivo monitoring of both ions with selective signals difficult. In addition, there is still no efficient water-soluble molecular probe for the simultaneous detection of Hg(II) and MeHg. Therefore, a water-soluble and biocompatible FL probe, with distinguishable emission for simultaneous sensing of Hg(II) and MeHg, is crucial for the visualization of both species in vivo. It is also a prerequisite for monitoring mercury methylation and dynamic transformations of both species in native biological contexts. Herein, a double-response FL probe (E)-4'-(3-(4-(dimethylamino)phenyl)acryloyl)-3'-hydroxy-[1,1'-biphenyl]-3-carbaldehyde (DPAHB) was synthesized for the simultaneous sensing of Hg(II) and MeHg. This probe was highly selective for both species with distinguishable FL signals at different wavelengths without any interference. With good water-solubility and biocompatibility, DPAHB was successfully applied to the visualization of methylation and transformations of the two species in both cells and zebrafish.