Five distinct crystal forms of rifaximin (α, β, γ, δ and ε) were identified and characterized by x-ray powder diffraction, solid state 13C NMR, and HATR-IR spectroscopy. Changes in the crystal structure may produce differences of 2 to 3 orders of magnitude in the rate of intrinsic dissolution, solubility and bioavailability of rifaximin. Alteration of the pharmacokinetic parameters is of particular interest; the Cmax values of the crystal forms range from 1.1 to 1085.31 ng ml-1 and the AUC0-24 h values range from 10 to 4795 ng h ml-1. These findings are relevant to the therapeutic use of rifaximin.