In trout hepatocytes, hypotonic swelling is followed by a compensatory shrinkage called regulatory volume decrease (RVD). It has been postulated that extracellular ATP and other nucleotides may interact with type 2 receptors (P2) to modulate this response. In addition, specific ectoenzymes hydrolyze ATP sequentially down to adenosine, which may bind to type 1 receptors (P1) and also influence RVD. Accordingly, in this study we assessed the role of extracellular nucleoside 5'-tri- and diphosphates and of adenosine on RVD of trout hepatocytes. The extent of RVD after 40 min of maximum swelling was denoted as RVD₄₀, whereas the initial rate of RVD was called v_RVD. In the presence of hypotonic medium (60% of isotonic), hepatocytes swelled 1.6 times followed by v_RVD of 1.7 min^-1 and RVD₄₀ of 60.2%. Five µM of either ATP, UTP, UDP or ATPS (P2 agonists) increased v_RVD 1.5-2 times, whereas no changes were observed in the values of RVD₄₀. Addition of 100 µM of suramin or cibacron blue (P2 antagonists) to the hypotonic medium produced no effect on v_RVD but a 53-58 % inhibition of RVD₄₀. Incubation of hepatocytes in the presence of either 5 µM of [³²P]ATP or [³²P]ATP induced the extracellular release of [³²P]Pi (0.21 nmol 10^-6 cells min^-1) and [³²P]Pi (approx. 8 10^-3 nmol 10^-6 cells min^-1), suggesting the presence of ectoenzymes capable of fully dephosphorylating ATP. Concerning the effect of P1 activation on RVD, 5 µM adenosine both in the presence and absence of 100 µM NBTI (a blocker of adenosine uptake) decreased RVD₄₀ by 37-44% whereas 8-phenyl theophylline, a P1 antagonist, increased RVD₄₀ by 15%. Overall, results indicate that ATP, UTP and UDP, acting via P2, are important factors promoting RVD of trout hepatocytes, whereas adenosine binding to P1 inhibits this process.