The present study was undertaken to determine the effect of nucleosides on nuclear and cytoplasmic maturation of mouse oocytes. Oocyte-cumulus complexes (OCCs) were collected from large antral follicles 4 h after eCG-hCG treatment and cultured in maturation medium with or without nucleosides (4 ribo- and 4 deoxyribonucleosides) for 12 h. A majority of the oocytes examined developed to the metaphase-II stage, and the same result was found with in-vivo matured oocytes. However, mitochondrial membrane potential (MMP) was significantly lower in the oocytes matured in the presence of nucleosides than in the nucleoside-free controls. Oocyte MMP increased in vivo between 8 to 12 h after hCG injection, whereas no increases in MMP were observed in oocytes matured in the presence of nucleosides. Oocyte MMP was significantly lower only when OCCs were exposed to nucleosides for the latter 8 h of IVM. When OCCs were exposed to adenosine during the latter 8 h of IVM, MMP was lower compared with in-vivo matured oocytes, whereas a mixture of other ribonucleosides (guanosine, cytidine and uridine) did not affect the level of MMP. The developmental competence of oocytes exposed to adenosine during the latter 8 h of IVM was lower after parthenogenetic activation due to the lower pronuclear formation of the oocytes. These observations indicate that adenosine inhibits increases in oocyte MMP during the latter half of meiotic maturation and detrimentally affects cytoplasmic maturation.