NicKit™ p.s.o. has been developed for reducing the size of DNA probes to an optimal length for in situ hybridization, without the problem of over- or under- digestion encountered with other methods. The procedure involves a brief U.V. irradiation of probe DNA using a transilluminator or hand-held U.V. lamp followed by enzymatic digestion using a specially prepared endonuclease. The phosphodiester bond at pyrimidine dimers formed by U.V. irradiation is cleaved, resulting in average DNA lengths of 400 bases or less. Probe DNA can be subsequently labeled with PHOTOPROBE® Biotin or the FastTag® system. The NicKit™ p.s.o. reagents can treat up to 300 µg of DNA.