To reduce the fraction \( \frac{48}{64} \) to its lowest terms, we should divide both the numerator and the denominator by their greatest common divisor (GCD).
The GCD of 48 and 64 is 16. Therefore, we should divide both the numerator and the denominator by 16:
\[ \frac{48 \div 16}{64 \div 16} = \frac{3}{4} \]
So, the correct operation to write the fraction \( \frac{48}{64} \) in lowest terms is to divide the numerator and denominator by 16.