The impact of metallicity on the Cepheid Period-Luminosity ( P-L ) relation is investigated using HST ACS V and I images of M101 . Variations in the reddening-free Wesenheit parameter ( W ) , which is employed as a proxy for luminosity , are examined as a function of the radial distance from the center of M101 ( and thus metallicity ) . We determine that there is no dependence of the slope on metallicity . However , the intercept is found to depend on metallicity by \gamma _ { VI } = -0.33 \pm 0.12 mag dex ^ { -1 } and \gamma _ { VI } = -0.71 \pm 0.17 mag dex ^ { -1 } using 2 and 3 sigma rejection criteria , respectively . Sigma-clipping impacts the derived metallicity dependence , and the 2-sigma criterion applied likely mitigates blending , particularly in the crowded inner regions of M101 . A metallicity-corrected distance for M101 is obtained from 619 Cepheids ( \mu = 28.96 \pm 0.11 ) , a result that agrees with the recently determined SN Ia distance . The metallicity effects described can be bypassed by working at near and mid-infrared wavelengths ( e.g. , the Carnegie Hubble Program ) .