AbstractThe development of a virus is programmed by a series of negative and positive controls which determine the timing and the segment on either of the two DNA strands (lorr) to be transcribed into specific messenger RNA's. Bacteriophage λ provides one of the most deeply studied systems for following the development of lysogenic viruses. In the lysogenic repressed state, only 2–4% of the λ genome is expressed. Thispc‐cI‐rexregion is transcribed leftward to produce a repressor protein which prevents any further transcription by blocking theoLandoRoperators flanking thecI‐rexoperon (figs. 1, 2). Thisnegativecontrol is relieved by destruction of the repressor, and the result is the “induction” of viral development. The earliest post‐induction or postinfection events are the leftward transcription of thepLoLN region from strandland the rightward transcription mainly of thepRoR‐xsegment from strandr. The N product acts as apositivecontrol, permitting a leftward transcription beyond gene N and a rightward transcription of genescII‐O‐P and also Q. Theint‐xissystem controls the excision of the λ genome, whereas the act of rightward transcription and the products of genes O and P initiate the replication of λ DNA. The product of gene Q, still anotherpositivecontrol, stimulates rightward transcription of the late genes which control the synthesis and assembly of the phage heads and tails as well as cell lysis. Among other types ofnegativecontrol are the possible competition between the two divergent transcriptions originating in regionx, the “antirepressor” effect of thexproduct, and the interference between the two convergent transcriptions which collide in the central b2 region. The majority of controls are based on protein‐DNA interactions and can be modified by mutations. For instance, transcription can be rendered independent of negative repressor control either by constitutive,v, mutations which decrease or abolish the affinity of theooperators for the repressor or by insertion of new promoters–e.g., c17orric‐ on the “downstream” side of the operator. The need for the positive N and Q controls may also be obviated by mutations in the N‐ or Q‐dependent promoter or terminator elements.The specific DNA structure within the controlling sites is not known. However, a remarkable coincidence was observed; namely, the occurrence of pyrimidine‐rich clusters in those segments of the individual DNA strands acting as templates for RNA synthesis. This observation, which pertains to all studied DNA's, including those of phages T2, T3, T4, T5, T6, T7, λ, and ϕ 80, formed the basis for a proposal that implicates pyrimidine‐rich clusters in the initiation, control and/or termination of transcription, and also in the determination of the preferred strand and, consequently, the orientation of transcription. General considerations regarding the possible role of the structural singularities, especially those represented by the pyrimidine clusters, in the bipartite structur