RESULTS AND DISCUSSION We generally find the DNA yields to exceed those of isolates obtained using phenol/chloroform extractions and ethanol precipitation. In general the samples contain very little RNA. The DNA samples are of sufficient quality for Southern blot analysis using a variety of restriction enzymes, including those active only in low salt conditions. We have used this method to analyze fragments of up to 20 kb. We include 0.1 mg BSA/ml in the restriction enzyme digestion to absorb any residual SDS, proteases, or other inhibitory elements. The procedure described above is now being used routinely in several mouse genetics laboratories. The reduced manual labor involved is perceived as an important benefit of the method. When problems were occasionally encountered, this was due to either too large a tissue sample, insufficient agitation during lysis, or insufficient agitation during dissolution of the DNA. If problems with restriction digestion are encountered, the option of a phenol/chloroform extraction followed by a reprecipitation is still open.