There are 4 things that can cause this:
1. You have the special attacks setting for that NPC set to A, which makes them immune to melee.
2. You are attempting to use a weapon that is either too high for your level (don't meet the required level for it), or you are the wrong class/race/deity to use it. Most likely this is your problem.
3. You are a GM and have #invul on.
4. You are a Divine Aura buff on.
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