Uncertainty in the metal abundance dependence of the Cepheid variable period- luminosity (PL) relation remains one of the outstanding sources of systematic error in the extragalactic distance scale and Hubble constant. To test for such a metallicity dependence, we have used the WFPC2 camera on the Hubble Space Telescope (HST) to observe Cepheids in two fields in the nearby spiral galaxy M101, which span a range in oxygen abundance of 0.7+-0.15 dex. A differential analysis of the PL relations in V and I in the two fields yields a marginally significant change in the inferred distance modulus on metal abundance, with d(m-M)/d[O/H] = -0.24+-0.16 mag/dex. The trend is in the theoretically predicted sense that metal-rich Cepheids appear brighter and closer than metal-poor stars. External comparisons of Cepheid distances with those derived from three other distance indicators, in particular the tip of the red giant branch method, further constrain the magnitude of any Z-dependence of the PL relation at V and I. The overall effects of any metallicity dependence on the distance scale derived with HST will be of the order of a few percent or less for most applications, though distances to individual galaxies at the extremes of the metal abundance range may be affected at the 10% level.
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