In the ‘minisequencing’ primer-extension method, the DNA synthesis reaction catalysed by the DNA polymerases is used to distinguish between sequence variants1. We have converted the mini-sequencing reaction principle into a microarray format, and shown experimentally that it discriminates more than tenfold better between homozygous and heterozygous genotypes than hybridization with allele-specific oligonucleotide probes in the same array format2. The minisequencing microarrays are manufactured by coupling 1 or 2 primers per mutation to be detected as 100-M spots at a density of 400 M on a glass surface using an ‘in-house’–constructed printing robot. The arrayed primers are allowed to anneal to templates amplified by multiplex PCR, and the polymorphic nucleotides are detected by extending the primers with labelled nucleotide analogues using a DNA polymerase. For reading the fluorescence signals on the microarrays, we use an in-house experimental multicolour fluorescence scanner or the commercial ‘ScanArray’ instrument. The genotypes are assigned by simple calculation of the ratios between the signals for normal and mutant nucleotides. We have applied our array-based minisequencing system to analyse SNPs in a set of candidate genes for their association with myocardial infarction in a case-control study in the Finnish population3. We found that allelic variants of PAI1 and GPIIIa genes contributed an additive risk of developing myocardial infarction. As an alternative to minisequencing, we have developed a method based on allele-specific extension of immobilized detection primers. We are using this method to screen regional population samples from Finland for 30 mutations of the ‘Finnish disease heritage’ and other recessive diseases to determine their population frequencies and to identify regional clusters of disease carriers. All the mutations, constituting both point mutations and small and large deletions, are distinguished unequivocally in both heterozygous and homozygous form by our fluorescence-based primer extension assay on microarrays. The fact that we are able to use our in-house genotyping system based on primer arrays of intermediate density in practice to generate tens of thousands genotypes is evidence for the robustness of the primer extension approach. Moreover, the specific primer extension reactions on the microarrays allows quantitative mulitplex mutation detection. The through-put of the system is only limited by the capacity of performing multiplex PCR amplifications. Based on our results, we are convinced that primer extension is a more promising reaction principle for future efficient genotyping on high-density DNA chips than hybridization-based approaches.