PMS is a hormone deficiency disease believed by many to produce changes in mood and behavior as well as physical symptoms due to the menstrual cycle. Anecdotal reports from PMS sufferers suggest that their behavior is sufficiently beyond their control to satisfy the 'substantial capacity' requirement, either from the aspect of their ability to appreciate the criminality of their conduct or to conform their conduct. The diminished capacity defense is of a more recent vintage and is not a total defense to the charge. In a jurisdiction which applies a rigid version of the M'Naghten rule, the outlook for an effective assertion of the PMS defense is not hopeful. Even when a PMS defense fails, however, there is a strong argument to be made for mitigating the sentence due to the offender's medical and psychiatric condition. Although there is considerable disagreement among authorities about the impact of an extra Y chromosome, defense attorneys in other parts of the world have introduced the XYY complement as a basis for insanity pleas. The problem facing the American defense attorney has been to lay a sufficiently firm foundation to permit the defense to be raised at all. The attorney should be prepared to use as much psychiatric testimony as possible to indicate the existence of a mental disease or defect that either arises out of the XYY condition or coexists with it. In the absence of such testimony, it will be difficult to persuade a judge to submit the issue to a jury. Given the procedure for committing persons found not guilty by reason of insanity to mental institutions, it may happen that a person with an XYY chromosome abnormality so acquitted may spend more time in a mental institution than he would have in prison, given that his condition is genetically based and currently not responsive to treatment. The most effective use of the XYY chromosome syndrome may be in mitigating the punishment. Sixty-eight footnotes are listed.