In order to elucidate the cues for, and the biochemical mechanisms of, the transition to ureogenesis in the gulf toadfish Opsanus beta, experiments on the effects of confinement/crowding were carried out. Confinement of toadfish to small volumes of water initiated a switch to nearly complete reliance on ureogenesis for nitrogen excretion within 24­48 h. Further experiments suggested that this switch was probably due to the physical confinement per se, rather than to a measurable build-up of ammonia in the water. However, the possibility of the response being triggered by a very low concentration of a pheromone-like substance was not excluded by our experimental design. The activities of several enzymes of ureogenesis, ornithine­citrulline transcarbamoylase, aspartate amino transferase and glutamine synthetase, increased in the liver of toadfish during confinement. Notably, glutamine synthetase activity increased almost fourfold within 24 h, and this increase preceded increases in urea excretion. A number of plasma and liver amino acid concentrations changed during confinement: there were declines in plasma asparagine, glutamate and glycine levels and an increase in plasma valine, as well as a decline in liver alanine and an increase in liver arginine concentrations. Liver glutamine was not detectable. When the amino acid data are taken together with the enzyme activity changes, it appears that the switch to ureogenesis occurs primarily upstream of the ornithine­urea cycle, at the level of supply of nitrogen to the pathway. The results are discussed in the context of the habitat of toadfish.