We are attempting to adapt the two-dimensional polyacrylamide gel technology to the search for mutations that after the electrophoretic mobility of proteins. These events are expected to have a frequency on the order of 10(-6). To this end, programs that run on the CytocomputerTM are being developed for comparing the pattern of the gel derived from a child's blood sample with those of the gels of corresponding samples from its parents. We anticipate examining thousands of such trios. Programs are described that perform background normalization, noise filtering, spot detection, gel registration, and, finally, compare the father/mother/child gel trios for the presence of unique protein moieties in the child that are consistent with a mutational event.