A procedure to screen for mutant clones obtained by oligonucleotide-directed mutagenesis has been developed. It is based on the preparation of phage containing supernatants from a number (100 or more) of randomly chosen mutagenized M13 plaques. Aliquots from these supernatants are mixed to obtain pools, each containing 10 phages. Heterogeneous single-stranded DNA is prepared from these pools and used as template in a "single letter" sequence according to the dideoxy chain terminator method. Thus, the pool(s) containing the mutated sequence and the mutated sequence itself is identified by sequencing the single-stranded DNAs of the 10 phages present in the selected pool.