Current-voltage (I-V) relationships of glutamate receptors activated by the non-NMDA receptor agonist, kainate (KA), were determined in Xenopus laevis oocytes injected with either calf or chick brain mRNA. In most injected oocytes (n = 44; 84%), I-V plots to 80 muM KA exhibited inward rectification; however, in some oocytes (n = 7; 16%), the KA-evoked membrane current showed only slight outward rectification. A comparison between the resting membrane properties of injected oocytes with the KA-evoked currents revealed that weak outward rectification was often observed in oocytes possessing predominant voltage-activated calcium-dependent chloride currents (I(Cl(Ca))). In these oocytes, replacement of extracellular calcium (2 mM Ca2+) with magnesium ions (Mg2+), or the addition of the chloride channel blocker, anthracene-9-carboxylic acid (500 muM to 1 mM A9C), reduced I(Cl(Ca)), and also altered the nature of the KA I-V plot revealing inward rectification. It is proposed that the responses mediated by expressed non-NMDA receptors may be influenced by the activation of endogenous calcium-dependent membrane currents in Xenopus laevis oocytes.