Abstract Experimental data on high negative interference (Chase and Doermann, 1958) are analyzed. On the basis of a model, the switch hypothesis, presented by Chase and Doermann (1958) , and some simplifying assumptions, a mathematical theory is developed which makes it possible to take high negative interference into account when analyzing crosses and related phenomena involving more than two closely linked genetic markers. Two parameters are involved in the theory: (1) the average length R of an area with high crossover frequency (switch area) and (2) the reciprocal value s of the mean number of crossovers per map unit in such areas. Their respective values in T4 are approximately R = 4 MU and s = 6 MU (MU = map unit). In the discussion of the theoretical aspects of high negative interference, it is shown that partial-replica models of a fairly general type can, at least qualitatively, account for the high negative interference phenomena described by Chase and Doermann (1958) . Moreover, it is shown that the partial-replica models predict various phenomena, such as: (1) induction of a switch area by infection with partial heterozygotes; (2) clonality of recombinants of a different type and with different characteristics than the one resulting from duplication of a recombined genome; (3) clonality of heterozygotes; (4) triparental high negative interference. The first phenomenon has been detected by Edgar (1957) . Clonality of recombinants of the type predicted is strongly suggested by the data published by Hershey and Rotman (1949) and by Epstein (1958) . The situation concerning the triparental high negative interference and the clonality of heterozygotes is not yet decided. In the Appendix, a mathematical treatment of the switch hypothesis is presented.
[1]
F. Stahl.
The effects of the decay of incorporated radioactive phosphorus on the genome of bacteriophage T4.
,
1956,
Virology.
[2]
N. A. Barricelli,et al.
An analytical approach to the problems of phage recombination and reproduction. III. Cross reactivation.
,
1961,
Virology.
[3]
Nils Aall Barricelli,et al.
An analytical approach to the problems of phage recombination and reproduction: I. Multiplicity reactivation and the nature of radiation damages
,
1960
.
[4]
M. Chase,et al.
High Negative Interference over Short Segments of the Genetic Structure of Bacteriophage T4.
,
1958,
Genetics.
[5]
S. Benzer.
The elementary units of heredity.
,
1956
.
[6]
R. Epstein.
A study of multiplicity-reactivation in the bacteriophage T4. I. Genetic and functional analysis of T4D-K12(lambda) complexes.
,
1958,
Virology.
[7]
A. D. Hershey,et al.
Genetic Recombination between Host-Range and Plaque-Type Mutants of Bacteriophage in Single Bacterial Cells.
,
1949,
Genetics.
[8]
C. Levinthal,et al.
Recombination in Phage T2: Its Relationship to Heterozygosis and Growth.
,
1954,
Genetics.