Stress-induced impairment in spatial learning depends on both tPA and plasminogen. Wild-type (n = 9), tPA-/- (n = 9), and plasminogen-/- (n = 8) mice were trained to locate a hidden platform located in the training quadrant submerged 1 cm below water surface. (A) Six learning trials (120-sec cutoff time) were carried out in 2 days. Probe trial (120 sec; B), during which the platform was removed, was performed on the next day to assess retention of the previously acquired information. After the procedures were completed, the animals were subjected to 21 days of restraint stress and their learning abilities reinvestigated (C and D), but this time the animals were trained to learn a different platform location. Stress caused learning impairment in wild-type but not in tPA-/- or plasminogen-/- mice (C). However, memory retrieval was not affected by stress (D). Numbers inside columns in B and D represent percent time the mice spent in the platform quadrant during the probe trial. **, P < 0.01.