To simplify this expression, first convert each of the exponents to a fraction:

16^(1/2) + 64^(2/3) - (1/81)^(-3/4)

Now, calculate each term separately:

16^(1/2) = √16 = 4

64^(2/3) = ∛64^2 = ∛4096 = 16

(1/81)^(-3/4) = (81/1)^(3/4) = 3^3 = 27

Now, substitute the values back into the expression:

4 + 16 - 27

Now, perform the subtraction:

4 + 16 - 27 = -7

Therefore, 16^(1/2) + 64^(2/3) - (1/81)^(-3/4) equals -7.