Gross skin reactions of mouse feet have been studied after one or two doses of x-rays. For split-dose irradiations a first dose of 1000 rads was used. The total dose for various fractionation intervals to produce a chosen level of skin reaction (integrated over 8 to 30 days) was determined. The dose increment (<tex-math>$D_{2}-D_{1}$</tex-math>) necessary to produce the same effect with a split dose (D2) as with a single dose (D1) was determined for the various intervals. The value of <tex-math>$D_{2}-D_{1}$</tex-math> is interpreted as being due to (1) prompt intracellular recovery from sublethal injury; (2) progression through phases of different sensitivity in the cell cycle of cells which had been partially synchronized by the first dose; and (3) an increase in basal cell number by repopulation. The dose increment in the first 24 hours was found to be 500 to 550 rads, and a further increment of 580 rads was required from 1 to 21 days. These values are in close agreement with the results of clone-counting experiments using the Withers technique on the same mice (Emery et al., 1969), and with repopulation rates reported previously in pigs (16) and in human skin (17).

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