Loud harmonics between 55 and 70 mph

I have a 98 Chevy S-10 4WD (ZR2) that required a rebuild of the transmission 9 months ago. It recently developed a very loud harmonic while driving between 55 and 70 mph. It sounds almost like a low groan. It is so loud that it hurts my ears. It runs fine otherwise; starts easily, same mpg, sounds normal at lower speeds. Oil change three weeks ago 50/50 blend. Not sure if I should be looking at the engine (possible valve crack) or the transmission.

When driving at speed, put the transmission into neutral. What happens to the sound?

Significantly less but not gone.

I would start with tires (uneven wear pattern, belt separations) and then worry about wheel bearings.

Can you tell if it is coming from front or rear/left or right? Swap the tires around to see if you can get the noise to move with it.

Does the sound change when you turn? E.g. does it lessen or disappear when you turn left or right.

Since the harmonic only occurs at speeds over 50 mph on the highway, turning is out of the question. I have been planning on having the tires rotated. The front ones look OK, but there is a little uneven wear. The sound seems to be coming from either the engine or the front area of the transmission.

U Joints!