Geographic and temporal variation of the transferrin blood plasma protein system in the meadow vole, Microtus pennsylvanicus, was investigated by use of starch gel electrophoresis. Twenty-four collecting areas were chosen so as to form a sampling transect of more than 1600 miles extending from Jamestown, North Dakota, to Nantucket, Massachusetts, with a shorter, more finely sampled transect from Linesville, Pennsylvania, to Coxsackie, New York. Of four fields regularly sampled for temporal variation, only one (Ithaca II), showed significance (P < 0.01) and this was because of a single frequency change in May 1966. Nine additional fields were irregularly sampled for temporal variation, but all differences were nonsignificant. It can be questioned whether the change of frequency for one sampling period in Ithaca II was an actual temporal shift and, therefore, at present the change will not be regarded as biologically significant. An analysis of variance on samples from three fields wit4in a mile of each other at Ithaca, New York, resulted in high significance. If larger subsamples had been collected from the other areas, statistically significant microgeographic differences would probably have also been found. In spite of microgeographic and temporal variation in gene frequencies, there was a significant west-east trend of frequencies from North Dakota to Cape Cod. Frequencies deviating farthest from the regression line represented trapping areas with no subsamples. Most of the rare alleles in the study were found in eastern New York, perhaps as a result of isolation due to a formerly more discontinuous vole habitat in the east than in the midwest. Four islands off the Massachusetts coast and one off Rhode Island were also sampled. Except for two Tuckernuck and Nantucket the transferrin frequencies were all different. Similarity in frequency and gel pattern suggests that voles from Nantucket have restocked Tuckernuck relatively recently. Four of the five islands also exhibit a high degree of or complete homozygosity of one of the alleles, indicating a tendency towards or an actual state of fixation on each of the four islands. INTRODUCTION Variation of the blood plasma proteins has been demonstrated in many animals, especially since the development of gel electrophoresis in the mid-1950's. Smithies (1955) was the first to show group variations in the serum protein patterns of Caucasian and of African races of man, using starch gel electrophoresis. Other workers began sampling several groups of animals, with a great concentration on domestic stock. The outstanding investigator in this regard is Ashton, who demonstrated serum protein differences in cattle (1957), in sheep (1958a), in horses (1958b), in Zebu cattle (1959b), and in pigs (1960). Ashton (1959a) also looked at foetal mortality and beta1 Present address: Department of Biological Science, Robert College, Bebek P.K. 8, Istanbul, Turkey.