How much horsepower will a stock 2000 S-10 4.6L rear end and tranny handle?

The stock rear end and transmission in a 2000 S-10 with the 4.6L engine aren't designed for significantly more power than the engine produces. The 4.3L V6 was the largest engine option for that year's S-10, so a 4.6L would be a swap, meaning the stock drivetrain is even more likely to be the weak link.

Therefore, there's no single definitive horsepower rating. It will depend on several factors, and exceeding the stock horsepower rating by any significant margin risks failure. You could easily damage or destroy the rear end gears, axles, transmission gears, or the differential with just a moderate horsepower increase.

Think of it this way: the components were engineered for the power output of the factory engine. Adding significant power without upgrades to the drivetrain is like putting a race car engine in a stock chassis—it's not built to handle the stress.

To get a more precise idea of what the stock components can reliably handle, you'd need to consult with experts familiar with S-10 modifications and drivetrain upgrades. They could provide a better estimate based on the specific components in your truck.