Estimate of the rate of germinal mutation in Man is difficult. Genic and chromosomic mutations must be considered separately. The only usable method, to avaluated the rates of genic mutation, is the direct method. The rate is estimated from the recording, at birth, of subjects with a particular phenotype due to a recent mutation, i.e. whose parents are normal. This mutation must be dominant with complete penetrance. In most of the cases, it is a dominant disease but a biochemical marker may also be used. This is a difficult method since there are many subjects to study and diagnosis errors are possible and the paternity is not always known. The rate of mutation of chromosomal aberrations may also measured. If we consider abnormalities of number, one has to know that the greatest majority results in early miscarriage; on the contrary, abnormalities of balanced structures are their detection is long and costly. The study of the variations of the mutation rate is, for those reasons, difficult. Methods of sequential analysis using "sentinel" phenotypes have factors which may modify the mutation rates are concerned, the effects of radiation are better known than those of chemical mutations in Man.