Make sure your large drawing contains no superfluous hatches (especially exploded hatches) or unused (unreferenced) blocks. Thaw and switch on all layers, zoom to full drawing. Do not forget the paperspace (layouts). Use PURGE to purge unused blocks and symbol table definitions (for nested blocks, several PURGE cycles may be needed, the commandline -PURGE version has more options). The AUDIT command can make more table entries purgeable.
There can be also invisible objects in your drawing - you have to make them visible first. The DBLIST command can help to identify these objects. They can be:
texts or attributes containing only "spaces"
faces with all edges set to invisible (some add-on applications make them)
blocks containing only invisible attributes
points with low visibility
Problem No.1 can be solved by setting the QTEXTMODE variable to 1; problem No.2 by setting the SPLFRAME variable; and problem No.3 by the ATTDISP variable. For the problem No.4, set the PDMODE variable to 3 and PDSIZE to 0. By temporary setting of these variables (and a regen) you can display the originally invisible entities. After modifications set the variables to their original values.
Make sure your blocks defined in the drawing contain really only the required symbols and not e.g. the whole drawing. This applies also for the dim-arrow blocks like _DotSmall or _Open.
Your drawing can also contain other non-graphical entities (custom objects, dictionaries, ...) coming from add-on applications (and the 'registered applications' themselves) or e.g. from the 'layer filters' function (frequent problem) or from excessive annotation scale lists. You can purge these using the corresponding functions (e.g. DeleteFilters, DBXremSL).
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