L‐Glutamate (L‐GLU) induced astrocyte swelling in a time‐ and concentration‐dependent, as well as Na+‐ and Ca2+‐dependent, and Cl‐‐independent manner. Swelling was prevented by MK‐801, cystine, and ouabain. Since L‐GLU swelling is ionically dependent, we determined the role of various ions in such swelling. Our results indicate that K+ uptake plays a major role in the mechanism of L‐GLU‐induced astrocyte swelling. Like swelling, K+ uptake is dependent on Ca2+ and Na+, but not on Cl‐. Likewise, K+ uptake was inhibited by MK‐801, cystine, and ouabain. The K+ channel blockers, Ba2+ and tetraethylammonium, partially prevented L‐GLU‐induced swelling. In addition to K+ channels, K+ influx may also be mediated through Na+/K+‐ATPase, as its activity is increased by L‐GLU uptake along with the required Na+. Taken together, the data suggest that K+ influx plays a key role in the mechanism of L‐GLU‐mediated astrocyte swelling. J. Neurosci. Res. 52:307–321, 1998. © 1998 Wiley‐Liss, Inc.