Lewontin has worked in both theoretical and experimental population genetics. A hallmark of his work has been an interest in new technology. He was the first person to do a computer simulation of the behavior of a single gene locus (previous simulation work having been of models with multiple loci). In 1960 he and Ken-Ichi Kojima were the first population geneticists to give the equations for change of haplotype frequencies with interacting natural selection at two loci. This set off a wave of theoretical work on two-locus selection in the 1960s and 1970s. Their paper gave a theoretical derivation of the equilibria expected, and also investigated the dynamics of the model by computer iteration. Lewontin later introduced the D' measure of linkage disequilibrium. (He also introduced the term "linkage disequilibrium", about which many population geneticists have been unenthusiastic.)