We present a method for the automatic generation of oligonucleotide probe sets for DNA microarrays. This approach is well suited particularly for specificity evaluation of designed probes in large data sets. Algorithms for probe preselection, hybridization prediction and probe selection are presented. Combinatorial techniques are introduced for the selection of probe sets of high differentiation capability even from sequence databases of homologous conserved genes. These techniques include the automatic generation of group specific probes and the design of exluding probes. A basic prototype was implemented including a shared memory parallelization and distribution. The principal applicability of our method to a database of very conserved sequence data was shown and the run-time performance estimated.