Transfer of the small gaseous molecules CO2 and NH3 across biological membranes, long thought to occur solely by simple diffusion, is now known to be facilitated by members of two multigene families: aquaporins (AQP) and rhesus (Rh) proteins. Although it is accepted that AQP1 and Rh proteins are involved in CO2 and NH3 transfer, respectively, the idea that a single channel can exhibit selectivity for both gases is controversial. Indeed, studies using the same in vitro model (human red blood cells) have provided evidence both for and against a role for Rh proteins as CO2 channels. Thus, this study was initiated to provide in vivo evidence for a dual function of Rh proteins as ammonia and CO2 channels. Here, we show that in zebrafish (Danio rerio), direct ammonia-CO2 competition experiments in adults or translational knockdowns of Rh proteins in larvae affects both ammonia and CO2 excretion. These results suggest that Rh proteins in zebrafish may be common pathways for transport of ammonia and CO2.