Employing mainly the technique of zone electrophoresis of enzymes to detect genetic differences in homologous proteins, the following projects are in progress and will be extended under the present application: 1. An estimation of genetic difference between species, based on measurement of the proportion of genetic loci which differ between species. Using the same data, the formula of Nei will be applied to estimate the number of nucleotide substitutions per locus. Additionally, rate of genetic change in evolution will be estimated between those species on which information is available about time of divergence. 2. The development of a quantitative taxonomy also based on the above data, to express the genetic difference between taxa. 3. Induction and detection of new mutations which alter electrophoretic mobility but allow retention of enzyme activity. An extension of this work will produce an estimate of the relative frequencies of neutral and non-neutral mutations. 4. Detection of altered forms of enzymes in suppressor mutants of bacteria, probably representing transcription across punctuation codons with resultant attachment of two contiguous polypeptides. Another ongoing project is the study of variation in activity of certain enzymes which modify chemical carcinogens and particularly the aryl hydrocarbon hydroxylases and epoxide hydrases. This work is being done in human subjects, with particular emphasis on the relation of the enzyme activities to resistance and/or susceptibility to chemically induced tumors, particularly carcinoma of lung and bladder.