The halotolerant cyanobacterium Aphanothece halophytica grown under non-stress (0.5 M NaCI) and stress condition (2.0 M NaCI) provided a maximal Na[superscript+]H[superscript +] exchange when the optical density of culture reached 0.5-0.9 (7[superscript th] day). The Na[superscript +]H[superscript +] exchange of Aphanothece was shown to be dissipated by protonophores, namely valinomycin and CCCP. Na[superscript +]H[superscript +] exchange was strongly inhibited by monensin. Orthovanadate and DCCD also inhibited Na[superscript +]H[superscript+] exchange. Amiloride, a Na[superscript +]H[superscript +] antiporterer inhibitor, showed inhibition of Na[superscript +]H[superscript +] exchange. The Na[superscript +]H[superscript +] exchange was sensitive to sodium azide, an ATP formation inhibitor. These results strongly favour the concept that respiratory energy is used for proton efflux and that the resulting proton motive force may be involved in Na[superscript +]H[superscript +] exchange. A role for antiport activity in pH regulation can also explain the activity of Na[superscript+]H[superscript +] exchange over a broad pH range extending to the alkaline condition (pH 5.0-10.0). The cation/H[superscript +] exchange activity was observed when either mono-valent cations Na[superscript +], K[superscript +], Li[superscript +]) or di-valent cations (Ca[superscript 2+] and Mg[superscript 2+]) served as a cation. The K[subscript m] values for Na[superscript +], Ca[superscript 2+], and Li[superscript +] were 23.7, 4.4 and 36.0 mM, respectively, whereas the Vmax values were 15.0, 14.5 and 16.0% fluorescence respectively.