Biologists were puzzled by the discovery of left-handed Z-DNA because it seemed unnecessary. Z-DNA was stabilized by the negative supercoiling generated by transcription, which indicated a transient localized conformational change. Few laboratories worked on the biology of Z-DNA. However, the discovery that certain classes of proteins bound to Z-DNA with high affinity and great specificity indicated a biological role. The most recent data show that some of these proteins participate in the pathology of poxviruses.