A least-squares method is described for refining the heavy atom parameters of an isomorphous replacement phase analysis, based upon minimizing the weighted sum of squares of the lack-of-closure errors for each derivative in turn, the phase angles having been determined earlier by the use of all derivatives at once. Conclusions based on trials with cytochrome C are described. A comparison is made between the mean figure of merit and the Kraut and least-squares R factors (RK and RL) as working criteria of phase analysis and refinement. It is observed that heavy atoms will refine in position correctly if their initial displacement is as much as half the nominal resolution. The behavior of substitution number, A, and radial falloff factor, B, under varying conditions is studied.