DOS 4.x

MS-DOS 4.0 was not the next step after MS-DOS 3.3. Chronoloically, MS-DOS 4.0 was released after MS-DOS 3.2 and before MS-DOS 3.3. 4.0 was instead an update to MS-DOS 2.0 that added multitasking. Or rather, attempted to add multitasking. It widely broke compatibility and caused regular freeze ups. Some of the problems were purposeful; such as not running on most IBM-PC clones. Microsoft quickly replaced it with 4.01 that helped but did not eliminate all the issues (certainly not the clone incompatibility). IBM wisely chose not to base its PC-DOS 4 on MS-DOS 4.0 and instead updated 3.3 to create PC-DOS 4.00. When MS-DOS 4.0 became infamous, IBM made a bugfix update to their PC-DOS 4.00 and released PC-DOS 4.01 (4.0 was IBM's first in-house DOS and had not help from Microsoft). PC-DOS 4.00 and 4.01 are indeed different from MS-DOS bearing the same version numbers. MS-DOS 4.0 was so infamous that makers of DOS clones did not use "4.0" as their version number. Digital Research skipped to "DR-DOS 5.0" (later causing their MS-DOS 5.0 clone to be labeled "6.0"). Novell DOS also skipped "4.0" and followed the same pattern as Digital Research. Since many customers chose to 'downgrade' to MS-DOS 3.3, Digital Research also improved their DR-DOS 3.3 clone and labeled it DR-DOS 3.41. Even Microsoft president Jon Shirley later said, "maybe we shouldn't have called it DOS 4.0".

So, if a game lists "MS-DOS 4.0" in its system requirements, that it is certainly significant.