ISOLA is set in the devastation immediately following the 1995 Kobe earthquake, and follows the wandering of Yukari Kamo (Yoshino Kimura) who has neither home nor family. Yukari does, however, have a rather powerful ability to read others' thought. This ESP has brought her to the brink of madness and suicide in the past, but through the use of strong medications, she is able to repress the many voices in her head. When we catch up with her, she has wandered into an ad-hoc rescue center brimming with Kobe citizens who have lost family and home. There she volunteers during the day and sleeps in a storage room during the nights.
Yukari's sleeping habits are eventually found out by Hiroko Nomura (Satomi Tezuka), a high school counselor in charge at the rescue center. Hiroko allows Yukari to stay at her home where Yukari soon comes across the thirteen drawings of trees which Hiroko is diligently analysing. Each of the thirteen drawings is the work of Chihiro Moritani (YĆ» Kurosawa), a student at Hiroko's high school and each tree respresents a different personality residing within Chihiro. Over the next few weeks, Yukari coincidentally encounters Chihro in several situations, though Chihiro appears to be a completely different person at each encounter. Through Yukari's persistent kindness, she is soon able to ask Chihiro about her multiple personalities, and Chihiro quickly draws out her own little "family" tree. The only personality which cannot be placed neatly into the tree is the 13th, the personality named ISOLA. When Yukari presses Chihiro for more information regarding ISOLA, Chihiro nervously scribbles out the name. Chihiro then explains that ever since the car accident which took the lives of her parents, she has been plagued by these multpile personalities. Through her ESP eye, Yukari sees Chihiro floating above her unconscious body lying beside the burning automobile. Yukari realizes that Chihiro had an "out of body" experience. (Not to mention "out of mind".)
When people start turning up dead, Yukari's first thought is that these are somehow tied to Chihiro, since all those killed had come into some form of contact with her. The viscious dog that barks loudly at Chihro is soon found with its throat slit. We then watch in disbelief as the high school girl who bullied Chihiro drowns herself in the depths of a toilet bowl (perhaps one of the more creative methods of suicide in Japanese film). The gym teacher who lashes out at a rebellious Chihiro soon commits a strange form of hari kiri with a yakitori skewer. And so on.
Yukari's curiosity into Chihiro's situation soon brings her into contact with Dr. Kazuhiko Manabe (Ken Ishiguro), a psychology professor at a local university whose personal research happens to be in out of body experience. His research came to a screeching halt, however, the night the Kobe earthquake caused the tragic death of a research assistant in the midst of their experiment and completely destroyed the research lab. Through their cooperative investigation into Chihiro and the string of bizarre deaths, Dr Manabe and Yukari soon discover that a darker, more malevolent force is possibly the cause of all the fatal mayhem. Their suspicion is soon justified when ISOLA herself eventually hunts them down.